All-trans retinoic acid suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats

All-trans retinoic acid (ATRA) has been reported to exert major effects on the immune system, including monocytes/macrophages. The present study was designed to determine whether ATRA would modulate macrophage-associated liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS) in rats. All-trans retinoic acid administration alleviated the liver injury and reduced the incidence of death following hepatic failure. Serum alanine aminotransferase (ALT) levels 5 h after, and survival rates within 12 h after the administration of LPS were significantly lower in the ATRA-treated group (134 ± 119 IU/L and 72.7%) compared with the control group (713 ± 411 IU/L and 18.2%; P < 0.05). Histological findings supported these results. These effects may be due to suppression of tumour necrosis factor-α (TNF-α) and superoxide anions produced by activated macrophages. Serum levels of TNF-α 1 h after LPS administration were significantly lower in the ATRA-treated group (60.5 ± 7.0 ng/mL) as compared with the control group (105.2 ± 39.3 ng/mL; P < 0.05). Formazan deposition that was generated by the perfusion of the liver with nitroblue tetrazolium, also suggested suppression of the release of superoxide anions from hepatic macrophages. These results suggest that ATRA acts as an immunomodulator in liver injury by suppressing the activation of liver macrophages.     

Carotid atherosclerosis and cardiovascular risk factors: a comparison of residents of a rural area of Okinawa with residents of a typical suburban area of Fukuoka, Japan

Areas of Japan are known worldwide for the longevity of their residents. Okinawa has the highest longevity in Japan and a low rate of death due to cardiovascular disease. We investigated carotid atherosclerotic (CA) risk factors in islands of I city in Okinawa prefecture and compared them with K town, a suburban area of Fukuoka prefecture in Kyushu, to determine the relationship between cardiovascular risk factors and carotid atherosclerosis. We investigated conventional cardiovascular risk factors in 1078 I city residents (375 men, mean age 63.7 and 703 women, mean age 60.0) in 2000 and 2364 K town residents (676 men, mean age 57.1 and 1688 women, mean age 53.0) in 1999. Carotid atherosclerosis was assessed by mean intima-media thickness (IMT) by B-mode ultrasound. The mean IMT was significantly lower in the residents of I city than in those of K town (P < 0.05). Total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels and smoking rate were also lower in I city than in K town. Body mass index (BMI) and triglyceride (TG) level were higher in I city than in K town. In I city, multiple regression analysis found independent relationships between carotid atherosclerosis and age, sex (male), hypertension, LDL cholesterol, high-density-lipoprotein cholesterol (HDL-C), and diabetes. The lower mean IMT is probably related to a lower lifetime burden of atherosclerotic risk factors, which may in turn be related to the longevity of Okinawa residents. BMI was not a cardiovascular risk factor, although LDL cholesterol was a common important risk factor.     

Association of Chlamydia pneumoniae antibody with the cholesterol-lowering effect of statins

To investigate the association between Chlamydia pneumoniae (C. pneumoniae) infection and atherosclerosis, we compared the effect of lipid-lowering drugs on carotid intima-media thickness (IMT) between patients who were positive and negative for C. pneumoniae antibodies. A total of 165 asymptomatic hypercholesterolemic patients were randomized to probucol (500 mg per day, n = 82) or pravastatin (10 mg per day, n = 83) and followed for 2 years. The 2-year change of IMT in the common carotid artery was the primary endpoint, while mean IMT change and major cardiovascular events were secondary endpoints. C. pneumoniae antibodies (IgA and IgG) were measured by enzyme-linked immunosorbent assay. The 50 patients without C. pneumoniae antibodies showed significant reduction of IMT progression (-19%), while no significant change of IMT was noted in the 115 antibody-positive patients (-6%). Significant inverse associations were found between the reduction of IMT progression and the C. pneumoniae IgA- and IgG-antibody index (P < 0.01 and 0.01, respectively). No significant differences in the reduction of serum total-cholesterol and LDL-cholesterol were found between antibody-positive and -negative patients. There was no significant difference of efficacy between probucol and pravastatin. These observations suggest that C. pneumoniae infection reduces the effect of lipid-lowering therapy on carotid atherosclerosis and that this organism may play a role in the progression of atherosclerosis.     

Continuing Medical Education Activity in Echocardiography

Article Title: The Origin and Clinical Significance of the Signal Opposite to the Mitral E‐Wave: A Simple and Novel Indicator of Left Ventricular Filling Pressure
(Echocardiography 2011;28:605)     

Transthoracic Tissue Doppler Assessment of Left Atrial Appendage Contraction and Relaxation: Their Changes with Aging

Aim: We assessed left atrial appendage (LAA) function using transthoracic tissue Doppler echocardiography (TDE), and examined the influence of aging on LAA contraction and relaxation. Methods: The subjects were 45 consecutive patients with heart disease and 110 healthy individuals. LAA wall motion velocity (LAAWV) at the tip of the LAA was measured using transthoracic echocardiography (TTE) and/or transesophageal echocardiography (TEE). Results: We successfully recorded and measured LAAWV using TTE in 105 (95%) of the 110 healthy subjects. When angle correction was applied for the Doppler beam in TTE, LAAWV during contraction (LAAWVc) measured by TTE closely correlated with that measured by TEE (r = 0.97), and LAAWV during relaxation (LAAWVr) measured by TTE closely correlated with that measured by TEE (r = 0.95). LAAWVc and LAAWVr measured by TTE correlated significantly with the LAA flow velocities during LAA contraction and LAA relaxation measured by TEE (r = 0.64, P < 0.001; r = 0.53, P = 0.001). In healthy subjects, although LAAWVc remained unchanged with aging, LAAWVr significantly declined with aging (r =?0.48, P < 0.001) and had a significant negative correlation with left atrial dimension and a significant positive correlation with transmitral flow and annulus velocity during early diastole. Conclusion: Transthoracic TDE can provide information on LAA function. LAA relaxation may be impaired with aging and may be accompanied by early diastolic left ventricular dysfunction and chronic overload to the left atrium. (Echocardiography 2010;27:839‐846)     

Increased frequency of IFN-gamma-producing peripheral CD8+ T cells with memory-phenotype in patients with chronic hepatitis C

To identify the capacity for cytokine production and the phenotypic characteristics of peripheral CD8(+) T cells in patients with chronic hepatitis C, 31 patients with chronic hepatitis C and 22 healthy controls were studied at the single cell level by three-color flow cytometry. Whole blood was stained with surface CD8, intracellular interferon-gamma (IFN-gamma), and interleukin-4 (IL-4), surface CD8, CD28, and intracellular IFN-gamma after stimulation with PMA plus ionomycin, and then surface CD8, CD45RA, and CD28. IFN-gamma-producing peripheral CD8(+) T cells were found frequently in patients than in controls (P < 0.05), whereas IL-4-producing peripheral CD8(+) T cells were not. Although the frequency of peripheral CD28(+)CD8(+) and CD28(-)CD8(+) T cells in patients was not different from that of controls, CD28(+)CD8(+) T cells exceeded CD28(-)CD8(+) T cells in the capacity for IFN-gamma-production after mitogenic stimulation (P < 0.01). In a more detailed analysis of the CD28(+)CD8(+) T cells, CD45RA(-)CD28(+)CD8(+) T cells, defined phenotypically as memory cells, were found frequently in patients than in controls (P < 0.05). There were no significant correlations between the frequency of IFN-gamma-producing peripheral CD8(+) T cells and hepatitis C virus RNA level or serum alanine aminotransferase level in patients. These data suggest that functionally T cytotoxic type 1 and memory CD8(+) T cells are predominant in the peripheral blood of chronic hepatitis C patients and that such activated CD8(+) T cells are associated with liver damage.     

Left atrial wall motion velocity measured by the velocity profile method with tissue Doppler echocardiography in normal subjects: its relation to aging

Purpose The aim of this study was to find a method for measuring left atrial wall velocity (LAWV) during atrial contraction using tissue Doppler echocardiography.Methods The velocity profile method was used to measure left atrial wall velocity at several sites in 64 healthy individuals aged 25–84 years. We attempted to find maximum left atrial wall velocity (LAWVmax) by mapping on four-chamber, two-chamber, short-axis, and long-axis views and studied the relations between maximum left atrial wall velocity, age, and peak velocity during atrial contraction in mitral or pulmonary venous flow.Results Left atrial wall velocity was varied by changing the position of the sampling volume. The velocity profile pattern was similar to the left ventricular wall velocity pattern near the mitral valve annulus in the left atrium. Left atrial wall velocity had a positive peak during atrial contraction when the sample volume was located in the cranial and dorsal area. Maximum left atrial wall velocity was obtained in 74% of cases with the two-chamber view. Maximum left atrial wall velocity in healthy subjects was 3.1 ± 0.7cm/s, and the duration of the atrial contraction was 112 ± 12ms. Maximum left atrial wall velocity increased slightly with age but was not significantly correlated with peak velocity during atrial contraction in mitral or pulmonary venous flow.Conclusions Left atrial wall velocity was measured by the velocity profile method in 64 healthy subjects aged 25–84 years. Maximum left atrial wall velocity increased slightly with age but was not significantly correlated with the peak velocity during atrial contraction in mitral or pulmonary venous flow.