Shearing-induced contact pattern formation in hydrogels sliding in polymer solution.

The contact of a hydrogel during the rotational shearing on a glass surface in concentrated polymer solution was observed in situ. Dynamic contact patterns that rotate in-phase with the rotational shearing of the gel were observed for the first time. The contact patterns with a periodicity in the circumferential direction appeared and became fine with the shearing time. The patterns appeared more quickly at an elevated sliding velocity, polymer concentration, and normal pressure. Furthermore, the softness of the gel also substantially influenced the characteristics of the patterns. The pattern formation was discussed in terms of the non-linear rheology of the polymer solution at the rotational soft interface.

Circulating tricarboxylic acid cycle metabolite levels in citrin-deficient children with metabolic adaptation, with and without sodium pyruvate treatment.

Citrin deficiency causes adult-onset type II citrullinemia (CTLN-2), which later manifests as severe liver steatosis and life-threatening encephalopathy. Long-standing energy deficit of the liver and brain may predispose ones to CTLN-2. Here, we compared the energy-driving tricarboxylic acid (TCA) cycle and fatty acid ß-oxidation cycle between 22 citrin-deficient children (age, 3-13years) with normal liver functions and 37 healthy controls (age, 5-13years). TCA cycle analysis showed that basal plasma citrate and α-ketoglutarate levels were significantly higher in the affected than the control group (p<0.01). Conversely, basal plasma fumarate and malate levels were significantly lower than those for the control (p<0.001). The plasma level of 3-OH-butyrate derived from fatty acid ß-oxidation was significantly higher in the affected group (p<0.01). Ten patients underwent sodium pyruvate therapy. However, this therapy did not correct or attenuate such deviations in both cycles. Sodium pyruvate therapy significantly increased fasting insulin secretion (p<0.01); the fasting sugar level remained unchanged. Our results suggest that citrin-deficient children show considerable deviations of TCA cycle metabolite profiles that are resistant to sodium pyruvate treatment. Thus, long-standing and considerable TCA cycle dysfunction might be a pivotal metabolic background of CTLN-2 development.

[Clinical Application of Methods for the Qualitative Evaluation of Lipid Abnormalities].

Recent lifestyle and social environment changes in Japan have been accompanied by increasing incidencerates of metabolic disorders, such as dyslipidemia and diabetes. Therefore, the rates of cardiovascular disease due to the progression of atherosclerosis are also increasing, and cardiovascular disease remains the leading cause of death in Japan. In particular, dyslipidemia, represented by hypercholesterolemia, hypertriglyceridemia, and hypoalphalipoproteinemia, is closely related to the onset and progression of atherosclerosis. Total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol have been used as quantitative markers of lipids to evaluate cardiovascular risks. However, these markers are not sufficient to fully assess the risks. Therefore, we focused on qualitative markers that represent lipid abnormalities, and examined the utility of qualitative lipids evaluation as clinical markers of atherosclerotic disorders. Previously, we reported that HDL and LDL subclasses and sterol markers are clinically important for evaluating the pathogenesis and risks of cardiovascular disorders. Moreover, lipoprotein subclasses may be useful as therapeutic markers for cardiovascular disorders, and oxysterols may also be useful as diagnostic markers for dementing disorders and diseases of the central nervous system. These issues remain to befully elucidated in the future.

[Secondary Dyslipidemia-Diagnosis of Drug-Induced Dyslipidemia-].

Secondary dyslipidemia has various causes. Drug-induced dyslipidemia is classified as secondary dyslipidemia. Recent lifestyle changes and the aging of the population have resulted in an increased inci- dence of dyslipidemia, accompanying that of metabolic disorders. Thus, various medications for metabolic disorders, including diabetes, hyperlipidemia, and hypertension, have been developed. Therefore, the fre- quency of drug-induced dyslipidemia in secondary hyperlipidemia is increasing. In clinical practice, primary dyslipidemia and common secondary dyslipidemia, such as endocrine diseases, hepatic and renal diseases, and immune disorders, must be excluded. Following this exclusion, the diagnosis of drug-induced dyslipidemia can proceed. In this review, we summarize the pathogenesis, diagnosis, and treatment of drug- induced dyslipidemia. [Review].

Lipid profile and atherogenic indices soon after birth in Japanese preterm infants.

AIM: The intra-uterine environment affects the risk of development of cardiovascular disease in adulthood. The aim of this study was to determine the influence of prematurity and foetal growth restriction on lipid metabolism, by assessing atherogenic indices soon after birth in preterm infants. METHODS: Blood samples were collected within 20 min of birth from 80 preterm infants with a gestational age of ≤35 weeks. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels were measured. The ratio of TC/HDLc, LDLc/HDLc and apoB/apoA1 were also calculated. Correlations between these indices and gestational age, birth weight and the standard deviation (SD) score for birth weight were also determined. RESULTS: Gestational age, birth weight and SD score for birth weight were negatively correlated with the TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios. CONCLUSION: In preterm infants, prematurity and poor foetal growth may influence lipid and apolipoprotein metabolism and affect atherogenic indices at birth.

Maze-solving in a plasma system based on functional analogies to reinforcement-learning model.

Maze-solving is a classical mathematical task, and is recently analogously achieved using various eccentric media and devices, such as living tissues, chemotaxis, and memristors. Plasma generated in a labyrinth of narrow channels can also play a role as a route finder to the exit. In this study, we experimentally observe the function of maze-route findings in a plasma system based on a mixed discharge scheme of direct-current (DC) volume mode and alternative-current (AC) surface dielectric-barrier discharge, and computationally generalize this function in a reinforcement-learning model. In our plasma system, we install two electrodes at the entry and the exit in a square lattice configuration of narrow channels whose cross section is 1×1 mm2 with the total length around ten centimeters. Visible emissions in low-pressure Ar gas are observed after plasma ignition, and the plasma starting from a given entry location reaches the exit as the discharge voltage increases, whose route converging level is quantified by Shannon entropy. A similar short-path route is reproduced in a reinforcement-learning model in which electric potentials through the discharge voltage is replaced by rewards with positive and negative sign or polarity. The model is not rigorous numerical representation of plasma simulation, but it shares common points with the experiments along with a rough sketch of underlying processes (charges in experiments and rewards in modelling). This finding indicates that a plasma-channel network works in an analog computing function similar to a reinforcement-learning algorithm slightly modified in this study.

Low serum carnitine level is associated with increased urinary carnitine excretion in late pregnancy.

BACKGROUND: Carnitine is essential for fatty acid metabolism. Free carnitine (FCA) is excreted in the urine in the glomerulus, but is partly reabsorbed by a carnitine transporter. The mechanism underlying the decrease in serum carnitine level during pregnancy is unclear. OBJECTIVE: To investigate whether low carnitine level is associated with increased renal excretion in pregnant women. METHODS: We recruited 43 healthy pregnant and 25 non-pregnant women. Total carnitine (TCA) and FCA levels were measured using the enzymatic cycling method, and the acylcarnitine (ACA) level was calculated. Fractional excretion (FE) was calculated as carnitine clearance divided by creatinine clearance. RESULTS: The mean TCA, FCA, and ACA levels were lower at 12 weeks of gestation in pregnant than non-pregnant women (P < .001); the levels decreased further at 36 weeks, reaching 39%, 36%, and 52% of those in non-pregnant women, respectively (P < .001). The FEs were 3-4-fold higher in pregnant women than non-pregnant women. Pregnant women had a lower serum FCA/TCA ratio than non-pregnant women (0.788 ± 0.098 vs 0.830 ± 0.074, respectively; P < .05), whereas the urine FCA/TCA ratio was similar between the groups. CONCLUSION: Low carnitine level is associated with increased renal excretion during late pregnancy.

[Genetic predisposition to dyslipidemia].

Lipid metabolism is regulated by several factors, such as apolipoproteins, lipoprotein receptors, enzymes, and transfer proteins. From the early 1980s until now, molecular biology has been developing rapidly. Hence, genetic analyses have accelerated all over the world. Using these techniques, many genetic investigations have been performed in large-scale studies, which revealed the close associations between genetic abnormalities of the above-mentioned factors and a variety of dyslipidemic disorders. In recent years, novel genes which regulate cholesterol metabolism were reported. For instance, proprotein convertase subtilisin kexin type 9 (PCSK9) and autosomal recessive hypercholesterolemia (ARH) were found as causal genes in patients whose phenotypes are similar to familial hypercholesterolemia. Niemann-Pick C1-Like 1 (NPC1L1), ATP-binding cassette (ABC) A1 (ABCA1), and G5/G8 (ABCG5/G8) were also identified as cholesterol transporters in intestinal epithelial cells and hepatocytes. NPC1L1 is recognized as a target of ezetimibe, a cholesterol absorption inhibitor classified into a new class of lipid-lowering agents. However, we have not been fully successful in identifying candidate genes for all dyslipidemias. In this review, we summarize major dyslipidemic disorders and their causal genes, pathosis, clinical features, diagnosis, and therapeutic approaches. Because it is difficult to analyze genetic abnormalities in clinical laboratories at present, simple and convenient procedures for genetic analyses are expected to be developed in the near future. Such techniques may reveal unknown pathologics for heritable dyslipidemias, which may lead to the search for potential drug targets.

Dynamic capabilities of maritime infrastructure: conceptual design of merchant vessels with usability in crisis.

Today's social infrastructure, e.g., transportation, medical services, energy supply and distribution, may become temporarily unable to provide functions due to the damage to buildings or excessive congestion resulting from threats, such as natural disasters, rising sea levels, pandemics. Maritime-based responses, typified by hospital ships, are drawing attention as a method to mitigate these effects. However, while designing emergency infrastructure, it is necessary to consider not only the value of these systems in emergencies but also during normal times. This study adopts the systems approach, a set of methods to conduct decision-making when complex stakeholders' relationships are involved. We focus on medical functions and propose a conceptual design for a flexible hospital ship with dynamic capability during emergencies as well as normal times. Specifically, we examine the optimal combination of ship type, size, navigation range during normal times, operations during emergencies, and contract approaches. Quantitative evaluation of utility during emergencies and economic efficiency are considered in tradeoff. In addition to the conventional cost-based study, we examined benefit-cost through ship sharing, in which ships are leased to the private sector as merchant vessels during normal times to generate revenue.

Higher concentration of 25-hydroxycholesterol in treatment-naïve patients with type 2 diabetes compared to healthy individuals.

BACKGROUND: Oxysterols are cholesterol oxidation derivatives with diverse biological activities. However, little is known about the oxysterol levels in treatment-naïve patients with type 2 diabetes. OBJECTIVE: We utilized gas chromatography-mass spectrometry to investigate the potential association between oxysterol concentrations and type 2 diabetes and atherosclerosis in treatment-naïve patients diagnosed with type 2 diabetes. METHODS: This case-control study enrolled 53 eligible patients with type 2 diabetes and 50 healthy volunteers. We compared serum oxysterol concentrations between the two groups; we examined the correlation between the oxysterol concentrations and the carotid plaque score in the type 2 diabetes group. RESULTS: Univariate analysis revealed significant differences in the concentrations of oxysterols (i.e., cholesterol-5α, 6α-epoxide; cholesterol-5ß, 6ß-epoxide; 7ß-hydroxycholesterol; and 25-hydroxycholesterol [25-HC]) and other cardiovascular risk factors between the two groups. The 25-HC concentration was almost twofold greater in the type 2 diabetes group than in the healthy volunteers (median [interquartile range]: 8.52 [6.37-11.26] vs. 4.58 [3.45-5.44] ng/mL). After adjusting for multiple covariates, such as age, body mass index, mean arterial pressure, and triglyceride, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol levels, only the concentration of 25-HC showed a significant association with type 2 diabetes. However, the univariate analysis failed to demonstrate any significant correlation between oxysterol concentrations and the carotid plaque score among individuals with type 2 diabetes. CONCLUSIONS: The levels of various oxysterols differ between treatment-naïve patients with type 2 diabetes and healthy individuals; the 25-HC level differs the most prominently.

Lipoprotein lipase concentration in umbilical cord blood reflects neonatal birth weight.

BACKGROUND: Insulin resistance (IR) is exacerbated during pregnancy via increases in insulin counterregulatory hormones. Maternal lipids are strong determinants of neonatal growth, although triglyceride-rich lipoproteins (TGRLs) cannot be transferred directly to the fetus through the placenta. The catabolism of TGRLs under physiological IR and the reduced synthesis of lipoprotein lipase (LPL) are poorly understood. We examined the association of maternal and umbilical cord blood (UCB)-LPL concentrations with maternal metabolic parameters and fetal development. METHODS: Changes in anthropometric measures and lipid-, glucose-, and insulin-related parameters, including maternal and UCB-LPL concentrations, were examined in 69 women during pregnancy. The relationship between those parameters and neonatal birth weight was assessed. RESULTS: Parameters reflecting glucose metabolism did not change during pregnancy, whereas those associated with lipid metabolism and IR changed markedly, particularly in the second and third trimesters. In the third trimester, the maternal LPL concentration gradually decreased, by 54%, whereas the UCB-LPL concentration was âˆ¼2-fold higher than the maternal LPL concentration. Univariate and multivariate analyses showed that the UCB-LPL concentration was a significant determinant of neonatal birth weight, together with placental birth weight. CONCLUSION: The LPL concentration in UCB reflects neonatal development under a decreased LPL concentration in maternal serum.

Anion-exchange HPLC separation of five major rabbit lipoproteins using a nonporous diethylaminoethyl-ligated gel with a perchlorate-containing eluent.

Rabbits are often used as experimental animals in studies of atherosclerosis and hyperlipidemia. Although rabbit lipoproteins can be quantitated by sequential ultracentrifugation, a simpler and more reproducible method is desirable for detailed analyses. The current study describes a method to analyze rabbit lipoproteins in plasma by anion-exchange high-performance liquid chromatography using a column filled with nonporous, diethylaminoethyl-ligated polymers. A solution of NaClO4 was used to adjust the ionic strength of the eluent. The method required only 15 µL of plasma and analysis was completed in 23 min. Five lipoprotein fractions (high-density lipoprotein, low-density lipoprotein, intermediate-density lipoprotein, very-low-density lipoprotein and chylomicrons) were eluted with step-wise increases in a concentration of NaClO4. The post-column eluate was reacted with an enzymatic reagent to determine total cholesterol, and the lipoprotein-cholesterol fraction was calculated according to relative peak areas in the chromatogram. The within-day and between-day assay coefficients of variation for lipoprotein cholesterol levels ranged between 0.436 and 7.143% and between 2.905 and 10.526%, respectively. Administering a high-fat diet increased lipoprotein-cholesterol concentrations by 6- to 77-fold. The method described here was nevertheless able to quantitate levels of lipoprotein-cholesterol in plasma samples from these rabbits. These results indicate that this method may be applied to lipoprotein studies using hyperlipidemic rabbit models.

[LDL-cholesterol homogeneous assays versus Friedewald's equation].

Low-density lipoprotein (LDL) is an important risk factor for coronary artery disease as well as ischemic stroke. In clinical practice, LDL-cholesterol (LDL-C) is calculated by Friedewald's equation or determined by homogeneous assays for LDL-C. Although Friedewald's equation has some limitations, it has been widely used for LDL-C measurement for nearly 40 years. On the other hand, the first LDL-C homogeneous assay was developed in the late 1990s. New reagents have appeared on the market one after another, and 12 homogeneous assays are now available in Japan; however, they measure LDL-C by different principles, which are not disclosed to the public. There is some debate about which method is superior for LDL-C measurement of clinical samples.

Evaluation of the mechanical behavior of bulk-fill and conventional flowable resin composites using dynamic micro-indentation.

The purpose of this research was to investigate the mechanical behavior of commercially available bulk-fill and conventional flowable resin composites using the dynamic micro-indentation method. The effect of inorganic filler content on mechanical properties was also assessed. Weight percentages of the inorganic filler in the resin composite were measured using the ashing technique. The results showed that dynamic hardness and elastic modulus tended to increase with inorganic filler content. Furthermore, the differences in mechanical properties between top and bottom surfaces were less pronounced in bulk-fill flowable resin composites compared with conventional flowable resin composites. In conclusion, the mechanical properties of bulk-fill flowable resin composites are affected by filler content. Moreover, bulk-fill flowable resin composites have a higher polymerization depth than conventional flowable resin composites when sample thickness is 4 mm.

Experimental evidence that phenylalanine is strongly associated to oxidative stress in adolescents and adults with phenylketonuria.

Few studies have looked at optimal or acceptable serum phenylalanine levels in later life in patients with phenylketonuria (PKU). This study examined the oxidative stress status of adolescents and adults with PKU. Forty PKU patients aged over fifteen years were enrolled, and were compared with thirty age-matched controls. Oxidative stress markers, anti-oxidant enzyme activities in erythrocytes, and blood anti-oxidant levels were examined. Nitric oxide (NO) production was also examined as a measure of oxidative stress. Plasma thiobarbituric acid reactive species and serum malondialdehyde-modified LDL levels were significantly higher in PKU patients than control subjects, and correlated significantly with serum phenylalanine level (P<0.01). Plasma total anti-oxidant reactivity levels were significantly lower in the patient group, and correlated negatively with phenylalanine level (P<0.001). Erythrocyte superoxide dismutase and catalase activities were higher and correlated significantly with phenylalanine level (P<0.01). Glutathione peroxidase activity was lower and correlated negatively with phenylalanine level (P<0.001). The oxidative stress score calculated from these six parameters was significantly higher in patients with serum phenylalanine of 700-800 µmol/l. Plasma anti-oxidant substances, beta-carotene, and coenzyme Q(10) were also lower (P<0.001), although the decreases did not correlate significantly with the phenylalanine level. Serum nitrite/nitrate levels, as stable NO products, were higher together with low serum asymmetric dimethylarginine, as an endogenous NO inhibitor. Oxidative stress status is closely linked with serum phenylalanine levels. Phenylalanine level in should be maintained PKU below 700-800 µmol/l even in adult patients.

Cross-sectional study of bone metabolism with nutrition in adult classical phenylketonuric patients diagnosed by neonatal screening.

The mechanism underlying the development of osteopenia or osteoporosis in longstanding phenylketonuria (PKU) remains to be clarified. We investigated the details of bone metabolism in 21 female and 13 male classical PKU patients aged 20-35 years. Vitamin D (VD), parathyroid hormone (PTH), bone turnover markers, and daily nutrient intake were examined. The patients had lower daily energy and protein intake than did the age-matched controls (22 women, 14 men), but their respective fat, VD, and calcium intake did not differ. Serum 1,25-dihydroxy VD and 25-hydroxy VD levels in female and male patient groups were significantly higher and lower than those in respective control groups (females, P < 0.001; males, P < 0.05 and P < 0.01, respectively). Serum intact PTH levels were significantly higher in the female patient group (P < 0.05). Urinary calcium levels in the patient groups were significantly higher than those of the control subjects (females, P < 0.001; males, P < 0.05). Bone resorption markers were significantly higher in patients than in controls, although bone formation markers were not different. Patient serum levels of osteoprotegerin-inhibiting bone resorption were significantly lower (females, P < 0.001; males, P < 0.01). None of the bone parameters correlated significantly with serum phenylalanine or nutrient intake. PKU patients exhibited lower VD status and more rapid bone resorption despite normal calcium-VD intakes.

Impacts of angiopoietin-like proteins on lipoprotein metabolism and cardiovascular events.

PURPOSE OF REVIEW: Angiopoietin-like proteins (Angptls) comprise a family of secreted glycoproteins with high homology to angiopoietins which are important regulators of angiogenesis. Angptl3 and Angptl4 inhibit lipoprotein lipase in mice. This article reviews recent human studies on Angptls and their effects on lipoprotein profiles and cardiovascular disease. RECENT FINDINGS: Population-based studies have indicated that loss-of-function mutations of Angptl3, Angptl4, and Angptl5 are associated with a low triglyceride concentration. Angptl3 concentration is positively correlated with HDL-cholesterol, but not with triglyceride, suggesting that Angptl3 regulates HDL metabolism by inhibiting endothelial lipase. Angptl4 concentration is correlated positively with triglycerides in patients with metabolic syndrome, although most studies have failed to find such a correlation. Angptl6 has no effects on lipoprotein profiles. Angptl3 is associated with atherosclerosis in coronary, carotid, and femoral arteries. Conflicting results have been obtained regarding whether the E40K variant (a loss-of-function mutation of Angptl4) is associated with an increased risk for cardiovascular disease, which may occur due to the lipid-independent actions of Angptl4. SUMMARY: Angptl3, Angptl4, and possibly Angptl5 are regulators of lipoprotein metabolism in humans. Whether inhibition of these Angptls will be useful for dyslipidemia to prevent cardiovascular disease remains to be elucidated in future studies.

Current Diagnosis and Management of Abetalipoproteinemia.

Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia. Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy. The deficiency of fat-soluble vitamins progressively develops into a variety of symptoms later in life, including hematological (acanthocytosis, anemia, bleeding tendency, etc.), neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.), and ophthalmological symptoms (e.g., retinitis pigmentosa). If left untreated, the disease can be debilitating and even lethal by the third decade of life due to the development of severe complications, such as blindness, neuromyopathy, and respiratory failure. High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications and improve the prognosis, enabling some patients to live to the eighth decade of life. However, it cannot fully prevent or restore impaired function. Novel therapeutic modalities that improve quality of life and prognosis are awaited. The aim of this review is to 1) summarize the pathogenesis, clinical signs and symptoms, diagnosis, and management of ABL, and 2) propose diagnostic criteria that define eligibility to receive financial support from the Japanese government for patients with ABL as a rare and intractable disease. In addition, our diagnostic criteria and the entry criterion of low-density lipoprotein cholesterol (LDL-C) ＜15 mg/dL and apoB ＜15 mg/dL can be useful in universal or opportunistic screening for the disease. Registry research on ABL is currently ongoing to better understand the disease burden and unmet needs of this life-threatening disease with few therapeutic options.

Comparison of the Japan Society of Clinical Chemistry reference method and CDC method for HDL and LDL cholesterol measurements using fresh sera.

OBJECTIVES: In 2009, the Japan Society of Clinical Chemistry (JSCC) recommended a reference method for the measurement of serum high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels. This automated method uses cholesterol esterase-cholesterol dehydrogenase to measure cholesterol levels in fractions obtained after ultracentrifugation and dextran sulfate/magnesium chloride precipitation. In the present study, using fresh samples, we compared the LDL-C and HDL-C levels measured using this method with those measured using the traditional Centers for Disease Control and Prevention (CDC)-beta-quantification (BQ) method. DESIGN: and methods: Using both the JSCC and CDC-BQ methods, LDL-C/HDL-C levels were measured in 47 non-diseased and 126 diseased subjects, whose triglyceride levels were lower than 11.29 â€‹mmol/L (1000 â€‹mg/dL). RESULTS: For LDL-C, the equation of the line representing the correlation between the two methods was y â€‹= â€‹0.991x + 0.009 â€‹mmol/L; r â€‹= â€‹0.999; and Sy/x â€‹= â€‹0.025 â€‹mmol/L, where x is the mean LDL-C level measured using the CDC-BQ method. Similarly, for HDL-C, the equation of the line representing the correlation between the two methods was y â€‹= â€‹0.988x + 0.041 â€‹mmol/L, r â€‹= â€‹0.999, and Sy/x â€‹= â€‹0.019 â€‹mmol/L, where x is the mean HDL-C level measured using the CDC-BQ method. CONCLUSIONS: The JSCC method agreed with the CDC-BQ method in cases of both non-diseased and diseased subjects, including those with dyslipidemia.