Abstract Background Inflammatory reactions and oxidative stress, which are important in progression of atherosclerosis, are reported to be increased in individuals with metabolic syndrome (MetS). On ...the other hand, adiponectin levels are lowered. Since effects of pitavastatin on these parameters have not been reported in hypercholesterolemic patients with MetS, the present study was conducted. Purpose To evaluate the effects of pitavastatin on inflammatory reaction, oxidative stress, and plasma adiponectin levels in hypercholesterolemic MetS patients in a multicenter trial. Methods This open-label, single group study was performed at 7 hospitals in Japan. Pitavastatin (2 mg/day) was administered to 103 consecutive patients with hypercholesterolemia, subdivided into MetS and non-MetS for 12 weeks. Blood samples were collected after overnight fasting at the start of treatment (baseline) and after 12 weeks. Results In the patients with MetS ( n = 69), mean values of plasma high-sensitivity C-reactive protein (hs-CRP) were significantly higher and mean values of plasma high-molecular-weight (HMW)-adiponectin significantly lower than in their counterparts without MetS ( n = 34). The baseline HMW-adiponectin and high-density lipoprotein cholesterol (HDL-C) values significantly correlated only in the MetS patients ( r = 0.318; p = 0.01). In an effectiveness analysis including 94 patients (62 with MetS, 32 without MetS), the level of hs-CRP was significantly decreased in patients with MetS during the drug treatment, whereas HMW-adiponectin did not change. When patients with MetS were divided into two subgroups according to the percent changes in HDL-C, significantly greater increase in HMW-adiponectin by pitavastatin treatment was observed in the HDL-C ≥10% increase subgroup than in the HDL-C <10% increase subgroup ( p = 0.009). Conclusion Twelve weeks administration of pitavastatin, in addition to the antihyperlipidemic effects, may be beneficial as an anti-atherosclerotic therapy in hypercholesterolemic patients with MetS, taking changes in hs-CRP and HMW-adiponectin into consideration. ClinicalTrials.gov identifier: NCT00444717.
A 56-year-old woman exhibited a high serum carbohydrate antigen (CA) 19-9 level of 2697IU/mL and was referred to our department. Cervical to pelvic computed tomography (CT) andpositron emission ...tomography/CT revealed swollen lymph nodes all over the body. Examinationof a transbronchial lung biopsy specimen satisfied the histological diagnosis of sarcoidosis. HerCA19-9 level spontaneously decreased to within the normal limit. She presented with fewfindings specific to sarcoidosis, which was diagnosed upon detection of high serum CA19-9. Therehave been sporadic reports of increased CA19-9 levels in sarcoidosis.
To further elucidate the molecular mechanisms underlying the transcriptional regulation of the GHRH receptor (GHRH-R) gene, hormonal regulation of the promoter activity of this gene was examined. An ...approximately 3-kb genomic fragment spanning the promoter region of the gene was sequenced and the transcription start site was determined by RT-PCR and RNase protection assay. A major start site was localized at -105 (relative to the translation initiation codon, ATG), and a pit-1 binding sequence characteristic of pituitary specific genes was found at -155 to -146. Deletion and mutation studies demonstrated this site to be functional. In the presence of dexamethasone, the GHRH-R promoter (from -2935 to -11) directed luciferase expression in MtT-S cells, a somatotropic cell line, but not in the PC12 cells that normally do not express GHRH-R. While T(3), all trans-RA, and 9cis-RA alone weakly enhanced the reporter gene expression, each of these substances was found to act as a synergistic enhancer in the presence of dexamethasone. Additional deletion and mutation analyses demonstrated a functional RA response element at -1090 to -1074. Two functional glucocorticoid response elements and a T(3) response element were found in an 80-bp 5'-flanking sequence of the pit-1 site. Interestingly, it is suggested that the 6-bp half-site AGGACA (from -209 to -204) functions as a 3'-half-site of T(3) response element as well as a 5'-half-site of one of the glucocorticoid response elements.
Theoretical calculations of the Sc 2p→3d→2p resonant X-ray emission spectroscopy (RXES) in ScF
3, ScCl
3 and ScBr
3 are performed with a ScX
6 (X = F, Cl and Br) cluster model. Effects of incident ...photon polarization, intra-atomic multiplet coupling and interatomic hybridization are taken into account. We pay attention to the intensity ratio of the RXES spectra arising from nonbonding states, which has mainly two peaks due to the crystal field splitting. From the change of the spectral intensity in RXES we can find that the highest energy structure of the main peaks in X-ray absorption spectroscopy (XAS) varies from almost pure e
g state to the e
g and t
2g mixed state according to the strength of multiplet effect and hybridization effect.
Abstract Background and purpose Metabolic syndrome (MetS) and chronic kidney disease (CKD) have both been reported as risk factors for cardiovascular events. The aim of this study was to assess the ...synergistic effect of MetS and CKD on atherosclerotic plaque and cardiovascular outcomes. Methods and subjects A total of 545 consecutive patients who underwent percutaneous coronary intervention (PCI) were divided into 4 groups based on the presence or absence of MetS and CKD. MetS was defined using the criteria of the Adult Treatment Panel III of the US National Cholesterol Education Program. CKD was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m2 . We analyzed the incidence of major adverse cardiac events (MACE), including cardiovascular death, nonfatal myocardial infarction, target lesion revascularization, and revascularization for new lesions. We also assessed coronary plaque characteristics of 204 patients using integrated backscatter intravascular ultrasound (IB-IVUS). Results MACE occurred more frequently in patients with both MetS and CKD (51.4%) than in the other groups, during the follow-up period (log-rank p < 0.001). In the IB-IVUS analyses, patients with both MetS and CKD exhibited greater plaque burden ( p = 0.003) with higher lipid content ( p = 0.048) compared to the other groups. In Cox analysis, both MetS and CKD proved to be independent predictors of MACE even after adjustment for confounding factors ( p = 0.018). Conclusions Comorbidity of MetS and CKD is an independent predictor of adverse cardiovascular outcomes in patients undergoing coronary intervention, an effect that may be attributed to coronary plaque instability.
Background Bilateral cavernous carotid aneurysms (CCAs) are very rare. A treatment strategy for symptomatic bilateral CCAs has not been established because of their complex pathogenesis. Here we ...report our treatment strategy and long-term results for 6 cases of symptomatic bilateral CCAs. Methods From January 2007 to December 2013, we treated 6 patients (2 men and 4 women; mean age at first treatment, 56.0 years) with symptomatic bilateral CCAs. Results All patients began to experience unilateral symptoms. Five of the 6 underwent high-flow bypass (HFB) with parent artery occlusion (PAO), and 1 received PAO only. Mean follow-up period after the first treatment was 61.3 months. All symptoms improved after the treatment. Five contralateral CCAs became enlarged during the follow-up period. Of these, 4 became symptomatic. One patient received superficial temporal–middle cerebral artery bypass with PAO, 2 received HFB with PAO, and 1 refused treatment. Final modified Rankin Scale scores were 0 in 4 patients, 1 in 1 patient, and 2 in 1 patient. There was no mortality in this series. Conclusions HFB with PAO is feasible as the first treatment for symptomatic bilateral CCAs. This treatment strategy steadies and simplifies future treatment of contralateral CCAs should they become symptomatic.
Background Although the safety of operations has generally improved in recent years, the mortality of extended operations for advanced gallbladder carcinoma (GBC) remains high, and the outcomes of ...patients with advanced GBC requiring major surgery are poor. In this study, a newly formulated original stage classification of advanced GBC was evaluated to clarify prognostic factors affecting long-term survival. Methods A total of 149 patients with resected GBC infiltrating beyond the propria muscle layer were analyzed retrospectively. These patients were classified into F0 ( n = 50), F1 ( n = 38), F2 ( n = 38), and F3 ( n = 23) according to the number of positive histopathologic factors, consisting of direct invasion to the liver, invasion to the hepatoduodenal ligament, and lymph node metastasis. Overall survival rates were compared with the Union Internationale Contre le Cancer TNM classification (6th edition). Results Overall 5-year survival rates of patients with F0, F1, F2, and F3 were 60%, 35%, 5%, and 0%, respectively. Significant differences were observed, except between F2 and F3. In 38 patients with F1, there were no significant differences between 13 patients with direct invasion to the liver, 4 patients with invasion to the hepatoduodenal ligament, and 21 patients with lymph node metastasis. Multivariate analysis revealed that F classification was the most important independent risk factor to predict survival. Conclusion Patients with advanced GBC are expected to survive long if only 1 of hepatic invasion, hepatoduodenal ligament invasion, or lymph node metastasis is positive.
Cyclosporine A (CsA) limits myocardial reperfusion injury and preserves mitochondrial integrity, but its influence on mitochondrial function has not been described in vivo. Auto-fluorescence of ...mitochondrial nicotinamide adenine dinucleotide and flavin adenine dinucleotide correlate with mitochondrial dysfunction. We hypothesized that CsA limits mitochondrial dysfunction and that fluorometry can quantify this influence.
Seventeen rabbits were studied: untreated (UnT, n = 7), CsA preinfarction (CsAp, n = 6), and CsA on reperfusion (CsAr, n = 4). Animals underwent 30 minutes of myocardial ischemia and 3 hours reperfusion. Infarct size was determined by staining. Nicotinamide adenine dinucleotide and flavin adenine dinucleotide fluorescence was continually measured in the risk area. The redox ratio was calculated flavin adenine dinucleotide(f)/(flavin adenine dinucleotide(f) + nicotinamide adenine dinucleotide(f)). Electron microscopy evaluated mitochondria morphology.
The infarct size by group was 39.1% +/- 1.7% in CsAp, 39.1% +/- 1.7% in CsAr, and 53.4% +/- 1.9% in UnT (p < 0.001). During ischemia, the CsAp group demonstrated less hypoxic reduction, with the redox ratio decreasing to 75.6% +/- 4.1% of baseline. The UnT and CsAr groups deceased to 67.1% +/- 4.0% and 67.2% +/- 3.6%, respectively (p < 0.005). During reperfusion the UnT group redox ratio increased to 1.59 +/- 0.04 times baseline. This increase was blunted in the CsAp (1.17 +/- 0.04, p = 0.026) and CsAr (1.35 +/- 0.02, p = 0.056) groups. Electron microscopy revealed reduced mitochondrial disruption in CsAp (19.7% +/- 7.6%) and CsAr (18.1% +/- 7.1%) rabbits compared with UnT (53.3% +/- 12.5%).
Fluorometric spectroscopy can be used in vivo to quantitatively assess the time course of CsA's influence on the mitochondrial dysfunction associated with myocardial ischemia and reperfusion.
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