Prevalence of Hepatitis A Immunity and Decision-tree Analysis Among Men Who Have Sex With Men and Are Living With Human Immunodeficiency Virus in Tokyo.

BACKGROUND: Hepatitis A virus (HAV) can be sexually transmitted. However, the level of HAV immunity among patients living with human immunodeficiency virus (HIV) in Japan is unknown. Determining the epidemiology of HAV infections among men who have sex with men (MSM) and who are living with HIV is essential for an HAV vaccination program. This study examined HAV immunity in patients living with HIV and applied the decision-tree analysis to explore the factors of immunoglobulin G (IgG)-hepatitis A (HA) antibodies in MSM living with HIV. METHODS: We examined the presence of IgG-HA antibodies among patients living with HIV from January to December 2017 in The Hospital of The Institute of Medical Science, The University of Tokyo. We recorded each patient's age, sex, mode of HIV transmission, year of HIV diagnosis, HAV vaccine status, history of HAV infection, and history of other infectious diseases. A decision-tree algorithm was used to reveal the factors and profiles most relevant to the anti-HAV prevalence. RESULTS: Overall, 378 MSM patients living with HIV were examined for IgG-HA antibodies. After excluding 24 patients who had received a HAV vaccine, the data of 354 MSM were analyzed (median age 45 years, interquartile range 39-51 years). Of the 354 patients, 60 (16.9%) were positive for IgG-HA antibodies. The HA positivity rate increased with patients' age, and age (> 63.5 years) was extracted as the most important variable by classification of the decision-tree algorithm. CONCLUSIONS: Our study, conducted just before the HAV outbreak among MSM in Tokyo, showed that age was the most relevant factor in anti-HAV prevalences. An extensive HAV vaccination program for MSM patients living with HIV is urgently needed, particularly for younger people.

Progression from stenosis to occlusion in the proximal native coronary artery after coronary artery bypass grafting.

Coronary artery bypass grafting (CABG) is an established treatment for multivessel coronary artery disease. However, problematic situations are occasionally encountered after CABG, such as disease progression in the native coronary artery with graft occlusion, which causes difficulty in revascularization. The purpose of this study was to evaluate changes in the native coronary artery after CABG. Between 2009 and 2012 in our institution, 351 patients underwent CABG, and 768 bypass grafts were anastomosed to non-occluded coronary arteries. Of these, 489 bypass grafts had available early postoperative angiographic results (≤6 months) suitable for assessment in this study. We defined malignant graft failure after CABG to be bypass graft occlusion and de novo complete occlusion of the target native coronary artery proximal to the graft anastomosis site. In the early angiographic results, 17 grafts were occluded (17/489; 3.5 %). Two of the grafts displayed malignant graft failure (a saphenous vein graft to the right coronary artery and a saphenous vein graft to the diagonal branch) (2 of 17 occluded grafts, and 2 of 489 studied grafts). Of the patent bypass grafts, 24 involved progression to occlusion in the proximal native coronary artery (19 saphenous vein grafts, 4 left internal thoracic artery grafts, and 1 right internal thoracic artery graft). Malignant graft failure was uncommon during short-term follow-up after CABG. At the same time, disease progression in the proximal native coronary artery from stenosis to occlusion following patent bypass grafting was relatively common, especially for vein grafts.

Impact of airflow limitation on carotid atherosclerosis in coronary artery disease patients.

BACKGROUND: Both airflow limitation and smoking are established cardiovascular risk factors. However, their interaction as risk factors for the development of atherosclerosis in coronary artery disease patients remains unclear. OBJECTIVES: To evaluate the effect of the interaction between airflow limitation and smoking status on the severity of carotid atherosclerosis. METHODS: We categorized the 234 enrolled patients with coronary artery disease into four groups: never-smokers with normal pulmonary function (group A), never-smokers with airflow limitation (group B), ever-smokers with normal pulmonary function (group C), and ever-smokers with airflow limitation (group D). RESULTS: The prevalence of airflow limitation in the enrolled patients was 23.1% (ever-smokers: 15.8%, never-smokers: 7.3%). The prevalence of severe carotid atherosclerosis was 28.2, 29.4, 41.3, and 45.9%, respectively, in the four groups (group D vs. group A, p = 0.035). Even after multivariate adjusting for confounding factors, ever-smokers with airflow limitation were independently associated with severe carotid atherosclerosis (odds ratio 2.89, 95% confidence interval, 1.19-7.00, p = 0.019). CONCLUSIONS: Ever-smokers with airflow limitation were significantly associated with severe carotid atherosclerosis among patients with coronary artery disease. These findings also provide additional insight into the correlation between airflow limitation and poor cardiovascular clinical outcomes.

Long-term clinical outcome after surgical or percutaneous coronary revascularization in hemodialysis patients.

BACKGROUND: Although revascularization via coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) has been widely performed, there are limited data on which procedure is best in hemodialysis (HD) patients. METHODS AND RESULTS: This 10-year follow-up study consisted of 997 HD patients electively undergoing coronary revascularization (CABG, n=210; PCI, n=787). With an adjustment for propensity scores with all baseline covariates, the incidence of major adverse cardiac events (MACE) was evaluated as a composite endpoint including all-cause death, non-fatal myocardial infarction (MI) and any revascularization. During the follow-up period, 465 MACE (death, n=325; non-fatal MI, n=45; revascularization, n=274) occurred. The 10-year freedom from MACE was higher in the CABG group compared to the PCI group (51.0% vs. 34.8%, adjusted hazard ratio [HR], 0.64; 95% confidence interval [CI]: 0.49-0.82, P=0.0003). On landmark analysis, adjusted HR of death was higher during the first 6 months after CABG compared to PCI (1.72; 95% CI: 1.04-2.79, P=0.036), but lower from 6 months onward (0.69; 95% CI: 0.48-0.97, P=0.033). When compared to patients treated with drug-eluting stent alone (n=345) in the PCI group, the CABG group still had an advantage for any revascularization (adjusted HR, 0.38; 95% CI: 0.22-0.62, P<0.0001), but not for MACE (adjusted HR, 0.86; 95% CI: 0.64-1.15, P=0.33). CONCLUSIONS: CABG was totally clinically advantageous compared to PCI in HD patients.

Sirolimus-eluting stent vs. everolimus-eluting stent for coronary intervention in patients on chronic hemodialysis.

BACKGROUND: Even in the drug-eluting stent era, adverse cardiac events, including restenosis after percutaneous coronary intervention (PCI), have been more frequently seen in patients on hemodialysis (HD) than in non-HD patients. The objective of this study was to compare the sirolimus-eluting stent (SES) and everolimus-eluting stent (EES) for prevention of adverse cardiac events, including restenosis, in HD patients. METHODS AND RESULTS: A total of 100 consecutive patients on HD who underwent PCI were enrolled and randomly assigned to receive SES or EES. Although there was no difference between the 2 groups in baseline patient and lesion characteristics, the angiographic restenosis rate at 8-month follow-up was 21.2% in the SES group and 8.7% in the EES group (P = 0.041). Significant differences were also seen in % diameter stenosis (%DS), minimal lumen diameter, and late lumen loss at 8-month follow-up (P = 0.0024, P = 0.0040, and P = 0.033, respectively). During the 1-year follow-up, major adverse cardiac events occurred in 11 (22.0%) patients in the SES group and in 5 (10.0%) patients in the EES group (P = 0.10). CONCLUSIONS: The use of EES was as safe as that of SES. Moreover, EES significantly prevented restenosis in patients on maintenance HD compared with SES.

Submucosal electrocoagulation for prolapsed hemorrhoids:a new operative approach to hemorrhoidal varices.

The results of submucosal electrocoagulation (SEC), a new radical operation for prolapsed hemorrhoids, in 403 patients with third- or fourth-degree hemorrhoids are reported. After resecting the anal skin tags that coexisted with prolapsed hemorrhoids, the hemorrhoidal varices could be resected and electrically coagulated through the wound without cutting the anal canal epithelium by using a fine needle-type electric knife. The results of this series indicated that SEC could dramatically reduce the incidence of the postoperative complications that sometimes occur after conventional hemorrhoidectomy, such as severe anal pain, massive anal bleeding and anal stenosis. Moreover, SEC could ensure that operated patients make an early return to social activities and have a satisfactory quality of life. Relapse of prolapsed hemorrhoids after SEC was rare.

Nitinol stenting improves primary patency of the superficial femoral artery after percutaneous transluminal angioplasty in hemodialysis patients: a propensity-matched analysis.

BACKGROUND: Although percutaneous transluminal angioplasty (PTA) has become a common therapeutic standard for peripheral artery disease (PAD), high restenosis rates in the superficial femoral artery (SFA) remain a major problem. Nitinol stent implantation is reported to reduce restenosis in SFA after PTA in the general population; however, little is known about whether the nitinol stent improves primary patency after PTA in hemodialysis patients who are at higher risk of revascularization failure. The aim of this study was to clarify the effects of nitinol stent implantation for primary patency in SFA after PTA in hemodialysis patients with PAD. METHODS: Eighty consecutive hemodialysis patients (167 SFA lesions) who underwent PTA with nitinol stents from January 2006 to January 2008 were compared with 64 hemodialysis patients (128 SFA lesions) who received stainless steel stents in the preceding 2 years. In the follow-up study to 2 years, incidence of restenosis, amputation, and all-cause mortality were analyzed. End points between the groups were examined with the Kaplan-Meier and log-rank methods. Prognostic values for end points were calculated by a Cox univariate analysis and Cox multivariable regression models. To statistically minimize the differences in each stent group, a propensity-matched analysis was also performed using the model including male gender, age, diabetes, hypertension, hyperlipidemia, smoking, incidence of ulcer/gangrene, and TransAtlantic Inter-Society Consensus (TASC) type C+D. RESULTS: The 2-year primary patency rate was 58% in the nitinol group vs 42% in the stainless steel group (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.39-0.84; P = .0045), despite a higher prevalence of TASC C+D lesion in the nitinol group (68% vs 49%, P = .0014). In 108 lesions matched after propensity score analysis, the primary patency for 2 years was 64% in the nitinol group vs 42% in the stainless steel group (HR, 0.39; 95% CI, 0.24-0.65; P = .0003). Cox multivariate models showed nitinol stent (HR, 0.42; 95% CI, 0.25-0.73; P = .002), age (HR, 1.04; 95% CI, 1.01-1.08; P = .031), and incidence of ulcer/gangrene (HR, 2.35; 95% CI, 1.17-4.75; P = .017) were independent predictors of restenosis. CONCLUSION: These data suggest that nitinol stent implantation improves primary patency in SFA after PTA compared with the stainless steel stent, even in hemodialysis patients with PAD.

Prognostic Importance of Multiple Nutrition Screening Indexes for 1-Year Mortality in Hospitalized Acute Decompensated Heart Failure Patients.

Background: The purpose of the study was to evaluate the impact of nutritional status on 1-year mortality in hospitalized patients with acute decompensated heart failure (ADHF). Methods and Results: We enrolled 457 hospitalized ADHF patients. Previously established objective nutritional indexes (controlling nutritional status [CONUT], prognostic nutritional index [PNI], geriatric nutritional risk index [GNRI], and subjective global assessment [SGA]) were evaluated at hospital admission. Malnutrition was defined as CONUT score ≥5, PNI score <38, GNRI score <92, and SGA scores B and C. The frequencies of malnutrition based on CONUT, PNI, GNRI, and SGA were 31.5%, 21.4%, 44.9%, and 27.8%, respectively. All indexes were related to the occurrence of 1-year mortality on univariate Cox regression analysis (P<0.05). We constructed a reference model using age, body mass index, systolic blood pressure, sodium concentration, and renal function on multivariable Cox regression analysis. Adding SGA to the reference model significantly improved both net reclassification improvement (NRI) and integrated discrimination improvement (0.344, P=0.002; 0.012, P=0.049; respectively). Other indexes (CONUT, PNI, and GNRI scores) significantly improved NRI (0.254, P=0.019; 0.273, P=0.013; 0.306, P=0.006; respectively). Conclusions: Nutritional screening assessed at hospital admission was appropriate for the prediction of 1-year mortality in hospitalized patients with ADHF.

Long-term outcome of percutaneous transluminal angioplasty in chronic haemodialysis patients with peripheral arterial disease.

BACKGROUND: Chronic haemodialysis patients are at an increased risk of peripheral artery disease (PAD). Although percutaneous transluminal angioplasty (PTA) has become a widely used therapeutic intervention for PAD, its outcome in haemodialysis patients remains poorly understood. The aim of this study was to clarify the long-term outcome of PTA as a primary treatment for PAD in haemodialysis patients. METHODS: Consecutive 118 haemodialysis patients with 205 lesions and 108 non-haemodialysis patients with 143 lesions who underwent successful PTA as a first-choice therapeutic option for PAD were enrolled. Outcome measures included primary patency, limb salvage and survival. RESULTS: Incidence of diabetes, history of coronary artery disease and femoropopliteal lesion were significantly more frequent in haemodialysis patients (P = 0.008, 0.005 and 0.0001, respectively), but critical limb ischaemia and TransAtlantic Inter-Society Consensus (TASC) lesion types occurred with comparable frequency in both groups. No patients had in-hospital complications. The 5-year primary patency, limb salvage and survival rates were significantly lower in haemodialysis patients (P = 0.01, 0.029 and 0.0024, respectively). On Cox multivariate analysis, haemodialysis was strongly predictive of amputation and all-cause death, but not of restenosis. In haemodialysis patients, TASC C+D lesion and ulceration/gangrene were independent predictors for restenosis and amputation. CONCLUSIONS: The long-term outcome after PTA may be fully acceptable in haemodialysis patients who are at the highest risk of cardiovascular disease. PTA is a useful therapeutic strategy in haemodialysis patients with PAD, but PTA for TASC C+D lesions remains controversial.

Hemorrhagic Pericardial Cyst Complicated with Constrictive Pericarditis.

Pericardial cysts are rare abnormalities and are usually asymptomatic. Although several case reports on their diagnosis and treatment have been published, those on hemorrhagic pericardial cysts remain limited. We herein report the case of a 70-year-old man with a hemorrhagic pericardial cyst complicated with constrictive pericarditis 2 years after the initial diagnosis.

Comparison of two dosing methods for immediate administration of tolvaptan in acute decompensated heart failure.

BACKGROUND: The clinical dosing method for tolvaptan in patients with acute heart failure (HF) is still unclear. We aimed to compare the differences in clinical effect between two dosing regimens: once-daily 7.5mg and twice-daily 3.75mg. METHODS: In this randomized trial, tolvaptan was administered within 12h from hospital admission. The primary outcome was the serial change in congestion scores measured every day from enrollment until dosing day 7. Outcomes including safety parameters were also evaluated. RESULTS: The subjects were assigned to either the once-daily 7.5mg dosing regimen (N=15) or the twice-daily 3.75mg dosing regimen (N=16). The time-course changes in body weight, serum sodium and creatinine levels, systolic blood pressure, daily urine output, and congestion scores were similar between the two groups. In the twice-daily 3.75mg dosing group, the serum sodium levels on days 3 and 4 were significantly (p<0.05) increased compared with those on day 1. The congestion scores significantly (p<0.05) decreased from day 2 to day 7 in both groups compared with those on day 1. However, the difference in the serial change in the congestion scores did not reach statistical significance. CONCLUSIONS: Our present results suggest that the early administration of tolvaptan within 12h after hospital admission significantly improved congestion from the first day after administration by either dosing regimen, i.e. once-daily 7.5mg or twice-daily 3.75mg in patients with acute HF.

Overexpression of Kruppel-like factor 7 regulates adipocytokine gene expressions in human adipocytes and inhibits glucose-induced insulin secretion in pancreatic beta-cell line.

We have identified Kruppel-like factor 7 (KLF7) as a new candidate for conferring susceptibility to type 2 diabetes. To ascertain the possible involvement of KLF7 in the pathogenesis of type 2 diabetes, we examined the functional roles of KLF7 in various types of cells. In human adipocytes overexpressing KLF7, the expression of adiponectin and leptin was decreased compared with that in control cells, whereas expression of IL-6 was increased. In the insulin-secreting cell line (HIT-T15 cells), the expression and glucose-induced secretion of insulin were significantly suppressed in KLF7-overexpressed cells compared with control cells, accompanied by the reduction in the expression of glucose transporter 2, sulfonylurea receptor 1, Kir6.2, and pancreatic-duodenal homeobox factor 1. We also found that the overexpression of KLF7 resulted in the decrease of hexokinase 2 expression in smooth muscle cells, and of glucose transporter 2 expression in the HepG2 cells. These results suggest that KLF7 may contribute to the pathogenesis of type 2 diabetes through an impairment of insulin biosynthesis and secretion in pancreatic beta-cells and a reduction of insulin sensitivity in peripheral tissues. Therefore, we suggest that KLF7 plays an important role in the pathogenesis of type 2 diabetes, and may be a useful target for new drugs to aid in the prevention and treatment of this disease.

Selecting effective siRNA sequences by using radial basis function network and decision tree learning.

BACKGROUND: Although short interfering RNA (siRNA) has been widely used for studying gene functions in mammalian cells, its gene silencing efficacy varies markedly and there are only a few consistencies among the recently reported design rules/guidelines for selecting siRNA sequences effective for mammalian genes. Another shortcoming of the previously reported methods is that they cannot estimate the probability that a candidate sequence will silence the target gene. RESULTS: We propose two prediction methods for selecting effective siRNA target sequences from many possible candidate sequences, one based on the supervised learning of a radial basis function (RBF) network and other based on decision tree learning. They are quite different from the previous score-based siRNA design techniques and can predict the probability that a candidate siRNA sequence will be effective. The proposed methods were evaluated by applying them to recently reported effective and ineffective siRNA sequences for various genes (15 genes, 196 siRNA sequences). We also propose the combined prediction method of the RBF network and decision tree learning. As the average prediction probabilities of gene silencing for the effective and ineffective siRNA sequences of the reported genes by the proposed three methods were respectively 65% and 32%, 56.6% and 38.1%, and 68.5% and 28.1%, the methods imply high estimation accuracy for selecting candidate siRNA sequences. CONCLUSION: New prediction methods were presented for selecting effective siRNA sequences. As the proposed methods indicated high estimation accuracy for selecting candidate siRNA sequences, they would be useful for many other genes.

Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy.

To search for a gene(s) conferring susceptibility to diabetic nephropathy (DN), we genotyped over 80,000 gene-based single nucleotide polymorphisms (SNPs) in Japanese patients and identified that the engulfment and cell motility 1 gene (ELMO1) was a likely candidate for conferring susceptibility to DN, in view of the significant association of an SNP in this gene with the disease (intron 18+9170, GG vs. GA+AA, chi(2) = 19.9, P = 0.000008; odds ratio 2.67, 95% CI 1.71-4.16). In situ hybridization (ISH) using the kidney of normal and diabetic mice revealed that ELMO1 expression was weakly detectable mainly in tubular and glomerular epithelial cells in normal mouse kidney and was clearly elevated in the kidney of diabetic mice. Subsequent in vitro analysis revealed that ELMO1 expression was elevated in cells cultured under high glucose conditions (25 mmol/l) compared with cells cultured under normal glucose conditions (5.5 mmol/l). Furthermore, we identified that the expression of extracellular matrix protein genes, such as type 1 collagen and fibronectin, were increased in cells that overexpress ELMO1, whereas the expression of matrix metalloproteinases was decreased. These results indicate that ELMO1 is a novel candidate gene that both confers susceptibility to DN and plays an important role in the development and progression of this disease.

Selecting effective siRNA sequences based on the self-organizing map and statistical techniques.

Short interfering RNA (siRNA) has been widely used for studying gene functions in mammalian cells but varies markedly in its gene-silencing efficacy. Although many design rules/guidelines for effective siRNAs based on various criteria have been reported recently, there are only a few consistencies among them. This makes it difficult to select effective siRNA sequences in mammalian genes. Here, we propose a new method for selecting effective siRNA target sequences on the basis of the self-organizing map (SOM) technique and statistical significance analyses for a large number of effective siRNAs. In the proposed method, the score is defined as a gene degradation measure. The effectiveness for the proposed method was confirmed by evaluating effective and ineffective siRNAs for recently reported genes (12 genes, 172 siRNA sequences) and comparing with other reported scoring methods. The size (value) of this score is closely correlated with the degree of gene degradation, and the score can easily be used for selecting high-potential siRNA candidates. The evaluation results indicate that the proposed method would be useful for many other genes. It will therefore be useful for selecting siRNA sequences in mammalian genes.

Unfractionated Heparin during the Interruption of Antiplatelet Therapy for Non-cardiac Surgery after Drug-eluting Stent Implantation.

OBJECTIVE: Heparin is not recommended to be administered during the interruption of antiplatelet therapy for non-cardiac surgery. However, there are insufficient data to determine the value. The purpose of the present study was to evaluate the clinical results of the administration of unfractionated heparin during the interruption of antiplatelet therapy in non-cardiac surgery patients who had previously undergone drug-eluting stent (DES) implantation. METHODS: We retrospectively identified 210 elective non-cardiac surgical procedures that were performed with the administration of unfractionated heparin during interruption of all antiplatelet therapies in patients who had previously undergone DES implantation. Heparin was administered during the perioperative period in accordance with the local practice guideline at out institution. We examined the clinical outcomes within 30 days of surgery. RESULTS: The mean number of implanted DESs was 2.1±1.3. No major adverse cardiac events (including cardiac death, definite stent thrombosis, and non-fatal myocardial infarction) occurred in any of the 210 cases within 30 days of surgery. Four of the 210 cases (1.9%) required reoperation for bleeding within 30 days of surgery. CONCLUSION: Our data showed the potential for the perioperative management with unfractionated heparin administration in Japanese patients who had previously undergone DES implantation who required non-cardiac surgery with the interruption of all antiplatelet therapies.

Impact of the statin escape phenomenon on long-term clinical outcomes in patients with acute myocardial infarction: Subgroup analysis of the Nagoya Acute Myocardial Infarction Study (NAMIS).

BACKGROUND: Statins are reportedly effective in the primary and secondary prevention of cardiovascular disease, mainly due to their ability to aggressively reduce low-density lipoprotein cholesterol (LDL-C) levels. However, patients sometimes exhibit the so-called "statin escape" phenomenon. The purpose of our study was to investigate the impact of the statin escape phenomenon on long-term clinical outcomes in patients with acute myocardial infarction (AMI). METHOD: This was a subgroup analysis of 1144 patients from the Nagoya Acute Myocardial Infarction Study (NAMIS) treated between January 2004 and December 2012. We analyzed 660 patients who initiated statin treatment after AMI. Statin escape phenomenon was defined as an increase in the LDL-C levels during the 9-month treatment period by >10% of the initial values after 4 weeks of initiating statin treatment. Patients were divided into two groups depending on whether they exhibited the statin escape phenomenon, with 474 patients in the non-escape group and 186 patients in the escape group. RESULT: Compared to the non-escape group, the escape group showed significantly lower LDL-C levels at 4 weeks after treatment initiation (81.3 ± 20.1 mg/dL vs. 101.1 ± 25.4 mg/dL, P < 0.01). By contrast, the escape group showed significantly higher LDL-C levels at 9 months after treatment initiation (105.8 ± 28.3 mg/dL vs. 90.3 ± 22.6 mg/dL, P < 0.01). Major adverse cardiac and cerebrovascular events (MACCE; a composite of all-cause death, MI, and stroke) were more frequent in the escape group than in the non-escape group (10.8% vs. 6.1%, P = 0.03). Multivariate analysis showed that statin escape phenomenon was an independent predictor of MACCE (hazard ratio: 2.02, 95% confidence interval: 1.11-3.66, P = 0.02). CONCLUSION: Statin escape phenomenon may be an independent predictor of long-term clinical outcomes in AMI patients.

Relation between paradoxical decrease in high-density lipoprotein cholesterol levels after statin therapy and adverse cardiovascular events in patients with acute myocardial infarction.

Statin therapy moderately increases high-density lipoprotein cholesterol (HDL-C) levels. Contrary to this expectation, a paradoxical decrease in HDL-C levels after statin therapy is seen in some patients. We evaluated 724 patients who newly started treatment with statins after acute myocardial infarction (AMI). These patients were divided into 2 groups according to change in HDL-C levels between baseline and 6 to 9 months after initial AMI (ΔHDL). In total, 620 patients had increased HDL-C levels and 104 patients had decreased HDL-C levels. Both groups achieved follow-up low-density lipoprotein cholesterol levels <100 mg/dl. Adverse cardiovascular events (a composite of all-cause death, myocardial infarction, and stroke) have more frequently occurred in the decreased HDL group compared with the increased HDL group (15.4% vs 7.1%, p = 0.01). Multivariate analysis showed that decreased HDL, onset to balloon time, and multivessel disease were the independent predictors of adverse cardiovascular events (hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.08 to 3.52; HR 1.05, 95% CI 1.01 to 1.09; and HR 2.08, 95% CI 1.22 to 3.56, respectively). In conclusion, a paradoxical decrease in serum HDL-C levels after statin therapy might be an independent predictor of long-term adverse cardiovascular events in patients with AMI.

Spontaneous development of hepatocellular carcinomas in the FLS mice with hereditary fatty liver.

The fatty liver Shionogi (FLS) mouse is an inbred strain that develops spontaneous fatty liver (hepatic steatosis) chronically without obesity. Here, we reported that the mice develop spontaneous hepatocellular tumors with high incidences. The mice with age of over 1 year frequently developed whitish protuberant nodules in the livers, which were histologically diagnosed as hepatocellular adenoma and/or carcinoma (HCC). An incidence of HCC was 12/30 (40%) in males at 15-16 months of age, while in females that was 0/36 at 13-16 months and 4/42 (9.5%) at 20-24 months. Furthermore, histological examinations showed that after 2-4 months of age mononuclear cell infiltration and clusters of foamy cells appear in the fatty liver with elevated serum alanine aminotransferase, suggesting presence of inflammatory responses and liver injury. These observations show that the FLS mice develop hepatocellular tumors following steatohepatitis. The mouse might be a good animal model for investigating liver tumor and non-alcoholic steatohepatitis.

Acute intracerebroventricular administration of either carboxyl-terminal or amino-terminal fragments of agouti-related peptide produces a long-term decrease in energy expenditure in rats.

We investigated if agouti-related peptide (AgRP), an endogenous antagonist of melanocortin receptors (MC3-R and MC4-R), effects energy expenditure in rats. Fragments of the carboxyl-terminal, AgRP (83-132), and the amino-terminals, AgRP (25-51) and AgRP (54-82), were administered intracerebroventricularly (ICV). Food intake, body weight and fat weight changes were measured 5 and/or 24 h after a single ICV injection of the fragments. Oxygen consumption and colonic temperature were measured as indices of energy expenditure, during 3 and 24 h after the ICV injections, respectively. An oral glucose tolerance test was performed 24 h after ICV AgRP (83-132) injection. Binding experiments were performed in HEK-293 cells that over-expressed human MC4-R. AgRP (83-132), but not AgRP (25-51) nor AgRP (54-82), induced a potent and long-lasting increase in the cumulative food intake. Both the carboxyl-terminal and amino-terminal AgRP fragments significantly decreased oxygen consumption and colonic temperature. Despite the absence of hyperphagia and cross-reactivities with MC4-R, AgRP (25-51) and AgRP (54-82) significantly increased body weight and epididymal/mesenteric fat weight. AgRP (83-132) did not affect glucose and insulin responses to the oral glucose tolerance test. AgRP causes a potent and long-lasting decrease in energy expenditure; an effect that is exhibited by carboxyl-terminal fragments and amino-terminal fragments that lack antagonist activity at the MC receptors. This suggests that the amino-terminal region of AgRP plays a regulatory role in energy metabolism.