Association of statin therapy with reduced coronary plaque rupture: an optical coherence tomography study

OBJECTIVE: Statin therapy induces plaque regression and may stabilize atheromatous plaques. Optical coherence tomography (OCT) is a high-resolution in-vivo imaging modality that allows characterization of atherosclerotic plaques. We aimed to demonstrate the potential utility of OCT in evaluating coronary plaques in patients with or without statin therapy. METHODS: Patients undergoing cardiac catheterization were enrolled. We identified culprit lesions and performed intracoronary OCT imaging. Plaque lipid pool, fibrous cap thickness, and frequency of thin-cap fibroatheroma were evaluated using previously validated criteria. Macrophage density was determined from optical signals within fibrous caps. Presence of calcification, thrombosis, and rupture was assessed. RESULTS: Forty-eight patients were included (26 on statins, 22 without statins). Baseline characteristics were similar apart from lipid profile. Patients on statin therapy had lower total and low-density lipoprotein cholesterol concentrations (4.45+/-1.35 vs. 5.26+/-0.83 mmol/l, P=0.02; 2.23+/-0.78 vs. 3.26+/-0.62 mmol/l, P<0.001, respectively). Frequencies of lipid-rich plaque (69 vs. 82%), thin-cap fibroatheroma (31 vs. 50%), plaque calcification (15 vs. 5%) and thrombosis (15 vs. 32%), and fibrous cap macrophage density were comparable between statin and nonstatin groups (5.9 vs. 6.3%; all P=NS). Ruptured plaques were, however, significantly less frequent in patients on established statin therapy (8 vs. 36%; P=0.03) with a trend toward increased minimum fibrous cap thickness (78 vs. 49 microm; P=0.07). CONCLUSION: We demonstrated the use of OCT in plaque characterization and found that patients on prior statin therapy have reduced incidence of ruptured plaques and a trend toward thicker fibrous caps. This suggests that statins may stabilize coronary plaques.     

Efficacy of subintimal angioplasty/stent implantation for long, multisegmental lower limb occlusive lesions in patients unsuitable for surgery.

PURPOSE: To investigate the feasibility and clinical outcomes of subintimal angioplasty combined with stent implantation in patients with long, multisegmental occlusive lesions unsuitable for surgical treatment. METHODS: Between 2003 and 2005, 30 patients (23 men; mean age 68 years, range 49-82) with severe claudication (Rutherford category 3, n=12) or critical limb ischemia (CLI; Rutherford category 4 or 5, n=18) underwent subintimal angioplasty with primary stenting for long (mean 28+/-11 cm) total occlusion in the lower limb arteries. Bypass surgery was considered unsuitable owing to inappropriate anatomy or poor distal runoff in 14 (47%) patients, severe coronary artery disease 14 (47%), or poor general condition in 2 (6%). RESULTS: Technical success was achieved in 27 (90%) of 30 cases. The 3 technical failures were due to inability to advance the wire, to re-enter the distal lumen, and vessel rupture, respectively. Three (10%) complications occurred (1 perforation, 2 hematomas) but did not require surgery. After a mean follow-up of 13+/-7 months (range 3-28), 10 (37%) cases of restenosis were found in 27 patients. At 12 months, the primary patency rate was 52%, and the limb salvage rate was 83%. CONCLUSION: Combined use of subintimal angioplasty and stent implantation was performed safely, with a relatively high success rate and acceptable intermediate-term clinical outcomes in patients with multisegmental, long occlusions of the lower limb arteries. Therefore, this strategy can be considered an option for symptomatic relief and limb salvage in patients unsuitable for bypass surgery due to various reasons.     

Mass spectrometric identification of citrullination sites and immunohistochemical detection of citrullinated glial fibrillary acidic protein in Alzheimer's disease brains

Peptidylarginine deiminases (PADs) are posttranslational modification enzymes that convert protein arginine to citrulline residues in a calcium ion‐dependent manner. Previously, we reported the abnormal accumulation of citrullinated proteins and the increase in the amount of PAD2 in hippocampi from Alzheimer's disease (AD) patients. Moreover, glial fibrillary acidic protein (GFAP), an astrocyte‐specific marker protein, and vimentin were identified as citrullinated proteins by using two‐dimensional gel electrophoresis and MALDI‐TOF mass spectrometry. To clarify the substrate specificity of PADs against GFAP, we prepared recombinant human (rh)PAD1, rhPAD2, rhPAD3, rhPAD4, and rhGFAP. After incubation of rhGFAP with rhPAD1, rhPAD2, rhPAD3, and rhPAD4, citrullinated (cit‐)rhGFAP was detected by Western blotting. The citrullination of rhGFAP by rhPAD2 was unique, specific, and time dependent; additionally, rhPAD1 slightly citrullinated rhGFAP. We then generated eight anti‐cit‐rhGFAP monoclonal antibodies, CTGF‐125, ?128, ?129, ?1212, ?1213, ?1221, ?122R, and ?1224R, which reacted specifically with cit‐rhGFAP. Two of those eight monoclonal antibodies, CTGF‐122R and ?1224R, reacted with both cit‐rhGFAP and rhGFAP in Western blots. By using the CTGF‐1221 antibody and a tandem mass spectrometer, we identified the two independent citrullination sites (R270Cit and R416Cit) of cit‐rhGFAP. Immunohistochemical analysis with CTGF‐1221 antibody revealed cit‐GFAP staining in the hippocampus of AD brain, and the cit‐GFAP‐positive cells appeared to be astrocyte‐like cells. These collective results strongly suggest that PAD2 is responsible for the citrullination of GFAP in the progression of AD and that the monoclonal antibody CTGF‐1221, reacting with cit‐GFAP at R270Cit and R416Cit, is useful for immunohistochemical investigation of AD brains. © 2015 Wiley Periodicals, Inc.     

Potential signaling pathways of acute endurance exercise-induced cardiac autophagy and mitophagy and its possible role in cardioprotection

Cardiac myocytes are terminally differentiated cells and possess extremely limited regenerative capacity; therefore, preservation of mature cardiac myocytes throughout the individual’s entire life span contributes substantially to healthy living. Autophagy, a lysosome-dependent cellular catabolic process, is essential for normal cardiac function and mitochondria maintenance. Therefore, it may be reasonable to hypothesize that if endurance exercise promotes cardiac autophagy and mitochondrial autophagy or mitophagy, exercise-induced cardiac autophagy (EICA) or exercise-induced cardiac mitophagy (EICM) may confer propitious cellular environment and thus protect the heart against detrimental stresses, such as an ischemia–reperfusion (I/R) injury. However, although the body of evidence supporting EICA and EICM is growing, the molecular mechanisms of EICA and EICM and their possible roles in cardioprotection against an I/R injury are poorly understood. Here, we introduce the general mechanisms of autophagy in an attempt to integrate potential molecular pathways of EICA and EICM and also highlight a potential insight into EICA and EICM in cardioprotection against an I/R insult.     

Morphological relationship analysis of impacted maxillary canines and the adjacent teeth on 3-dimensional reconstructed CT images

Objective:To examine whether there is a relationship between maxillary canine impaction and the morphologic characteristics of the maxillary dentition, especially the root of the lateral incisor.Materials and Methods:In this study, we selected only patients with unilateral maxillary canine impaction to compare the morphologic characteristics of the dentition on the impaction side and the clinically normal eruption side. The sample size was decided to be 40 based on the pilot study. To minimize bias depending on sex and location of the maxillary canine impaction, we selected equal numbers (20) of boys and girls, and equal cases (20) of buccal impaction and palatal impaction. Under the aforementioned conditions, the mean age was 13.5 ± 2.3 years. The multislice spiral computed tomography images of these 40 subjects were converted into three-dimensional (3D) reconstructed images using the OnDemand 3D program (Cybermed Co, Seoul, Korea). Then we measured the morphologic characteristics of the individual teeth on the obtained 3D teeth images.Results:Length and volume of the maxillary lateral incisor''s roots were significantly smaller on the impaction side compared with the normal eruption side (P = 0.001 and P = 0.006, respectively). The width and volume of the canine''s crown were significantly greater on the impaction side compared with the normal eruption side (P = 0.020 and P < .0001, respectively).Conclusion:These results might help to prove the hypothesis that the smaller-sized lateral incisor roots and greater-sized canine crowns are the influential etiologic factors in maxillary canine impaction.     

Optimal management of biopsy-proven low-grade gastric dysplasia

Gastric adenocarcinoma generally culminates via the inflammation-metaplasia-dysplasia-carcinoma sequence progression. The prevalence of gastric adenomas shows marked geographic variation. Recently, the rate of diagnosis of low-grade dysplasia(LGD) has increased due to increased use of upper endoscopy. Many investigators have reported that gastric highgrade dysplasia has high potential for malignancy and should be removed; however, the treatment for gastric LGD remains controversial. Although the risk of LGD progression to invasive carcinoma has been reported to be inconsistent, progression has been observed during follow-up. Additionally, the rate of upgraded diagnosis in biopsy-proven LGD is high. Therefore, endoscopic resection(ER) may be useful in the treatment and diagnosis of LGD, especially if lesions are found to have risk factors for upgraded histology after ER, such as large size, surface erythema or depressed morphology. Fatal complications in endoscopic submucosal dissection(ESD) are extremely low and its therapeutic and diagnostic outcomes are excellent. Therefore, ESD should be applied preferentially instead of endoscopic mucosal resection.     

Long-Term Outcomes and Dynamics of Mutants Associated with Lamivudine-Adefovir Rescue Therapy in Patients with Lamivudine-Resistant Chronic Hepatitis B

Background/Aims

To investigate the association between the baseline profiles and dynamics of hepatitis B virus (HBV) DNA polymerase gene mutations and the long-term virological response of lamivudine (LAM)-adefovir (ADV) combination therapy in patients with LAM-resistant chronic hepatitis B.

Methods

Seventy-five patients who received LAM-ADV combination therapy for more than 12 months were analyzed. Restriction fragment mass polymorphism assays were used to detect and monitor the dynamics of LAM- and ADV-resistant mutations.

Results

The median duration of LAM-ADV combination therapy was 26 months (range, 12 to 58 months). The baseline mutation profiles, rtM204I (p=0.992), rtM204I/V (p=0.177), and rtL180M (p=0.051), were not correlated with the cumulative virological response, and the baseline HBV DNA level (p=0.032) was the only independent predictive factor for cumulative virological response. Tests for LAM- and ADV-resistant mutations were performed in 12 suboptimal responders in weeks 48 and 96. The population of rtM204 mutants persisted or increased in 8 of 12 patients, and rtA181T mutants newly emerged as a minor population in four patients until 96 weeks. Nevertheless, the viral loads progressively decreased during rescue therapy, and these dynamics did not correlate with virological response.

Conclusions

The baseline profile and dynamics of LAM-resistant mutations during LAM-ADV combination therapy are not associated with a virological response.