Molecular mechanisms of cholesteryl ester transfer protein deficiency in Japanese

Plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins. Since CETP regulates the plasma levels of HDL cholesterol and the size of HDL particles, CETP is considered to be a key protein in reverse cholesterol transport (RCT), a protective system against atherosclerosis. The importance of plasma CETP in lipoprotein metabolism was demonstrated by the discovery of CETP-deficient subjects with marked hyperalphalipoproteinemia (HALP). Genetic CETP deficiency is the most important and common cause of HALP in the Japanese. Ten mutations of the CETP gene have been demonstrated as causes of HALP, including two common mutations: an intron 14 splicing defect (Int14 + 1 G --> A) and an exon 15 missense mutation (D442G). The subjects with CETP deficiency show a variety of abnormalities in the concentration, composition, and function of both HDL and low density lipoprotein (LDL). CETP deficiency is considered a physiological state of impaired RCT, which may possibly lead to the development of atherosclerosis despite high HDL cholesterol levels. However, the pathophysiological significance of CETP in terms of atherosclerosis has been controversial. Epidemiological studies in Japanese-Americans living in Hawaii and Japanese in the Omagari area, where HALP subjects with an intron 14 splicing defect of the CETP gene are markedly frequent, have shown a relatively increased incidence of coronary atherosclerosis in CETP deficiency. On the other hand, the TaqIB polymorphism-B2 allele with low CETP mass and increased HDL cholesterol has been related to a decreased risk for coronary heart disease (CHD) in many studies, including the Framingham Offspring Study. The current review focused on the characterization of the Japanese subjects with CETP deficiency, including our recent findings.     

Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on paraoxonase and platelet-activating factor acetylhydrolase in human plasma and tissue fluid

We have previously shown that intravenous apolipoprotein (apo) A-I/phosphatidylcholine (apo A-I/PC) discs increase plasma high-density lipoprotein (HDL) concentration in humans. We have now studied the associated changes in two enzymes, paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH) that are carried in whole or in part by HDLs, and are thought to influence atherogenesis by hydrolyzing oxidized phospholipids in lipoproteins. Apo A-I/PC discs (40 mg/kg over 4 h) were infused into eight healthy males. Although plasma apo A-I and HDL cholesterol increased on average by 178 and 158%, respectively, plasma total PON and total PAF-AH concentrations did not rise. By the end of the infusion, HDL-associated PAF-AH had increased by 0.56 +/- 0.14 microg/mL (mean +/- S.D., P < 0.01), and nonHDL-associated PAF-AH had decreased by 0.84 +/- 0.11 microg/mL (P < 0.05). These changes were accompanied by an increase in the HDL-associated PAF-AH/apo A-I ratio from 0.19 to 0.35 (P < 0.05), and by a decrease in the nonHDL-associated PAF-AH/apo B ratio from 2.1 to 1.4 (P < 0.05). No changes in PON or PAF-AH concentrations were detected in prenodal lymph (tissue fluid), collected continuously from the leg. Our results show that the total concentrations of PON and PAF-AH in plasma are uninfluenced by plasma HDL concentration. PAF-AH transfers readily between HDLs and LDLs in vivo, and its distribution between them is determined partly by their relative concentrations and partly by HDL composition.     

Comparison between resection arthroplasty alone and resection arthroplasty with arthrodesis of the first MTP joint for rheumatoid forefoot deformities

It has been reported that nearly 90% of patients with rheumatoid arthritis (RA) have problems with their feet. Several methods of treating hallux valgus deformity in RA have previously been reported, including arthrodesis and joint resection, and good results have been observed with surgical procedures. In this report, we compare the clinical and radiological outcomes of resection arthroplasty alone (the first method) and resection arthroplasty with arthrodesis of the first MTP joint (the second method) for the treatment of forefoot deformities of RA patients. On clinical assessment, the American Orthopaedic Foot and Ankle Society (AOFAS) scale score significantly improved in both methods; however, the second method gave better results than the first method in relation to the footwear and alignment components. On radiographic assessment, in the first method there were no significant changes in the valgus angle (H–V angle) and the fifth metatarsal bone (M1/5) angle between preoperation and last follow-up. In contrast, these angles were decreased in the second method. One of the most important issues in the treatment of forefoot deformities in RA patients is to correct splaying foot deformity. We believe that the second method, which can correct splaying foot deformity, is currently the most reliable treatment method.     

A mitochondrial superoxide theory for oxidative stress diseases and aging

Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed ”the Superoxide Theory,” which postulates that superoxide (O₂^•−) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q₁₀) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.     

Assessing head and trunk symmetry during sleep using tri-axial accelerometers

Using two types of small, lightweight tri-axial accelerometers, we obtained evidence for the effectiveness of an approach for assessing head–trunk symmetrical or asymmetrical positions during sleep. First, we assessed the accuracy of our monitoring system in five healthy young adults (age range, 22–24 years). The participants wore acceleration monitors on the sternum and forehead; then spent 5?min in six different positions. Once accuracy was confirmed, we assessed head–trunk symmetry during night-time sleep in 10 healthy children (age range, 3–13 years) and 10 young adults (age range, 21–26 years) in their home environments. All participants wore the monitors during one night’s sleep in their homes. After computing head–trunk positions using the orientation data obtained by the accelerometers, head and trunk symmetry were evaluated. The head and trunk positions were correctly detected: the positional data from the trunk had 99% agreement, and the data from the head had 96% agreement. Both the young adults and children were observed to spend time with the head–trunk in asymmetric positions; however, the subjects changed position frequently so the asymmetrical postures were mobile. We concluded that the proposed monitoring system is a reliable and valid approach for assessing head–trunk symmetry during sleep at home.

• Implications for Rehabilitation

• We propose a head and trunk symmetry monitoring system using accelerometers.

• The proposed system could accurately identify head and trunk position.

• Asymmetrical positioning was seen in healthy participants but it was not immobile.

     

Laparoscopic liver resection for hepatocellular carcinoma with cirrhosis in a single institution

Background

In a statement by the second International Consensus Conference for Laparoscopic Liver Resection (LLR), minor LLR was confirmed to be a standard surgical practice, as it has become adopted by an increasing proportion of surgeons. However, it is unclear whether this applies to the more complex group of patients suffering from cirrhosis. Therefore, the aim of this retrospective study was to compare the feasibility and safety of LLR for hepatocellular carcinoma (HCC) between non-liver cirrhosis (NLC) patients and liver cirrhosis (LC) patients at a single high-volume laparoscopy center.

Methods

From the beginning of 2000 to the end of 2013, open liver resection (OLR) was performed in 99 HCC patients, and LLR was in 118. The HCC patients who underwent LLR were divided into NLC-LLR (n=60) and LC-LLR (n=58) groups, and we compare the short-term outcomes between them.

Results

There was no significant difference in the incidence of blood loss and transfusion requirements between the NLC-LLR group and the LC-LLR group, although wedge resection was mainly performed in the LC-LLR group. There was no significant difference in the complication rate between the two groups, and the remarkable finding was that there was a significantly lower incidence of postoperative ascites in the LC-LLR group than in the NLC-LLR group.

Conclusions

According to our experience, it appears that LLR for selected HCC patients with cirrhosis is a feasible and promising procedure that is associated with less blood loss and fewer postoperative complications, especially the incidence of postoperative ascites. Further investigations are clearly warranted.     

Ethanol Stimulates Immunoreactive Endothelin-1 and -2 Release from Cultured Human Umbilical Vein Endothelial Cells

The present study employed enzyme-immunoassay to examine the effect of ethanol on endothelin-1 and/or -2(ET1 + 2) release from human umbilical vein endothelial cells. Thirty minutes of exposure to ethanol increased the release of immunoreactive ET1 + 2 from cultured endothelial cells in a dose-dependent manner. However, ethanol at concentrations of less than 400 mM did not induce any LDH release from the endothelial cells. Trypan blue exclusion test revealed that 400 mM solution of ethanol decreased the cell viability to 7.7%. Thus, ethanol was found to directly stimulate ET1 + 2 release from cultured human umbilical vein endothelial cells. This reaction of vascular endothelial cells against ethanol may be related to ethanol-induced cardiovascular diseases such as hypertension, myocardial infarction and stroke, as well as fatal alcohol syndrome.