Purified eicosapentaenoic acid reduces small dense LDL, remnant lipoprotein particles, and C-reactive protein in metabolic syndrome.
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Biomedical subjects
Publications and source records attributed to Noriko Satoh.
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Postprandial hyperglycemia and hyperlipidemia are considered risk factors for cardiovascular disease. This study was designed to elucidate whether improving the postprandial state by voglibose, an alpha-glucosidase inhibitor, leads to the reduction of oxidative stress markers and soluble adhesion molecules in obese type 2 diabetic patients. A total of 30 Japanese obese type 2 diabetic patients were randomly assigned and treated for 3 weeks with either diet alone (the control group) or diet plus voglibose (0.9 mg daily) (the voglibose group) (n=15 each). Analysis of the diurnal metabolic profiles revealed a significant reduction of postprandial hyperglycemia and hyperlipidemia in the voglibose group relative to the control group (P<.05), despite the similar improvement in body mass index and hemoglobin A(1c) in both groups. Voglibose also decreased significantly the plasma levels of soluble intercellular adhesion molecule 1 and urinary excretion of 8-iso-prostaglandin F(2)alpha and 8-hydroxydeoxyguanosine (P<.01) and C-reactive protein (P<.05) relative to the control group. In conclusion, this study represents the first demonstration that voglibose reduces oxidative stress generation and soluble intercellular adhesion molecule 1 in parallel with the reduction of postprandial hyperglycemia and hyperlipidemia in obese type 2 diabetic patients.
Although red blood cells account for about 30% of total PAF-AH activity found in the blood, the physiological function of this enzyme is unknown. To understand the role and regulatory mechanism of this enzyme, we purified it from easily obtainable pig red blood cells. PAF-AH activity was mainly found in the soluble fraction of the red blood cells. Two peaks of enzyme activity appeared with increasing concentration of imidazole on column chromatography on nickel-nitroacetic acid (Ni-NTA) resin. We called these peaks of small and large enzyme activities fractions X and Y, respectively, and then further purified the enzymes by sequential chromatofocusing on Mono P and gel filtration on TSK G-3000. In the final preparation from fraction Y, two proteins bands corresponding to 26 kDa and 28 kDa were related to enzyme activity. Determination of the partial amino acid sequences of the proteins of 26 kDa and 28 kDa revealed that these proteins were identical to alpha(1) and alpha(2), respectively, both of which are catalytic subunits of Type I intracellular PAF-AH. On Western analysis, the 26 kDa and 28 kDa protein bands cross-reacted with specific monoclonal antibodies to alpha(1) and alpha(2), respectively. Since the apparent molecular weight of the natural enzyme was estimated to be about 60 kDa, the enzyme activity in fraction Y was thought to be that of a heterodimer consisting of alpha(1) and alpha(2). On the other hand, the enzyme activity in fraction X was thought to be that of a homodimer consisting of alpha(2). Other blood cells such as polymorphonuclear leukocytes and platelets only contained the alpha(2)/alpha(2) homodimer. It has been reported that the alpha(1)/alpha(2) heterodimer is poorly expressed in adult animals except for in the spermatogonium. Taken altogether, these results suggest that high expression of the alpha(1)/alpha(2) heterodimer is important for the physiological function of mature red blood cells.
To study the role of adiponectin, a novel adipocyte-specific secreted protein, on the pathophysiology of eating disorders, circulating levels of fasting adiponectin, leptin, insulin, and glucose were measured in 31 female patients with anorexia nervosa (AN) and in 11 with bulimia nervosa. Hormone levels were compared with 16 age-matched, normal body weight controls, six healthy constitutionally thin subjects, and nine obese subjects. Moreover, changes in levels were reevaluated after nutritional treatment and weight gain in 13 patients with AN. Serum adiponectin concentrations in AN and bulimia nervosa were significantly lower than those in normal-weight controls. These results were unexpected because the levels were high in constitutionally thin subjects and low in obese subjects, which provide a negative correlation with body mass index (BMI) and body fat mass. In contrast, serum leptin levels correlated very well with BMI and fat mass among all the patients and controls. The insulin resistance was significantly low in AN and high in obese subjects. The concentrations of adiponectin after weight recovery increased to the normal level despite a relatively small increase in BMI. These findings suggest that abnormal feeding behavior in the patients with eating disorders may reduce circulating adiponectin level, and weight recovery can restore it.
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As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at approximately 58% compared with a peak at approximately 42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at approximately 42%, relatively low compared with that of protein-coding cDNAs.
Sickness evokes various neural responses, one of which is activation of the hypothalamo-pituitary-adrenal (HPA) axis. This response can be induced experimentally by injection of bacterial lipopolysaccharide (LPS) or inflammatory cytokines such as IL-1. Although prostaglandins (PGs) long have been implicated in LPS-induced HPA axis activation, the mechanism downstream of PGs remained unsettled. By using mice lacking each of the four PGE receptors (EP1-EP4) and an EP1-selective antagonist, ONO-8713, we showed that both EP1 and EP3 are required for adrenocorticotropic hormone release in response to LPS. Analysis of c-Fos expression as a marker for neuronal activity indicated that both EP1 and EP3 contribute to activation of neurons in the paraventricular nucleus of the hypothalamus (PVN). This analysis also revealed that EP1, but not EP3, is involved in LPS-induced activation of the central nucleus of the amygdala. EP1 immunostaining in the PVN revealed its localization at synapses on corticotropin-releasing hormone-containing neurons. These findings suggest that EP1- and EP3-mediated neuronal pathways converge at corticotropin-releasing hormone-containing neurons in the PVN to induce HPA axis activation upon sickness.
The platelet-activating factor-acetylhydrolase (PAF-AH) is an enzyme which catalyzes the hydrolysis of acetyl ester at the sn-2 position of PAF. The family of PAF-AHs consists of two intracellular isoforms (Ib and II), and one secreted isoform (plasma). These PAF-AHs show different biochemical characteristics and molecular structures. Plasma PAF-AH and intracellular isoform, II degrade not only PAF but also oxidatively fragmented phospholipids with potent biological activities. Among these PAF-AHs, plasma PAF-AH has been the target of many clinical studies in inflammatory diseases, such as asthma, sepsis, and vascular diseases, because the plasma PAF-AH activity in the patients with these diseases is altered when compared with normal individuals. Finding a genetic deficiency in the plasma PAF-AH opened the gate in elucidating the protecting role of this enzyme in inflammatory diseases. The most common loss-of-function mutation, V279F, is found in more than 30% of Japanese subjects (4% homozygous, 27% heterozygous). This single nucleotide polymorphism in plasma PAF-AH and the resulting enzymatic deficiency is thought to be a genetic risk factor in various inflammatory diseases in Japanese subjects. Administration of recombinant plasma PAF-AH or transfer of the plasma PAF-AH gene improves pathology in animal models. Therefore, substitution of plasma PAF-AH would be an effective in the treatment of the patients with the inflammatory diseases and a novel clinical approach. In addition, the detection of polymorphisms in the plasma PAF-AH gene and abnormalities in enzyme activity would be beneficial in the diagnosis of the inflammatory diseases.
OBJECTIVE: Thiazolidinediones (TZDs), a class of insulin-sensitizing agents used clinically to treat type 2 diabetes, are also antiatherogenic. This study was designed to elucidate the relationship between the antiatherogenic and antidiabetic effects of pioglitazone, a TZD, in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 136 Japanese type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (30 mg daily for 3 months) (n = 70) and the untreated control group (n = 66). The changes in glycolipid metabolism as well as plasma high-sensitivity C-reactive protein (CRP), leptin, adiponectin, and pulse wave velocity (PWV) were monitored to analyze the relationship between the antiatherogenic and antidiabetic effects of pioglitazone. RESULTS: The pioglitazone treatment significantly reduced hyperglycemia, hyperinsulinemia, and HbA(1c) levels and increased plasma adiponectin concentrations relative to the control group (P < 0.01). It also significantly decreased CRP and PWV (P < 0.01). The antiatherogenic effect was observed in both the nonresponders showing <1% of reduction in HbA(1c) (n = 30) and responders showing >1% of reduction (n = 40). ANCOVA revealed that treatment with pioglitazone was associated with a low CRP and PWV, independent of the changes in parameters related to glucose metabolism. CONCLUSIONS: This study represents the first demonstration of the antiatherogenic effect of pioglitazone in both nonresponders and responders with respect to its antidiabetic effect and suggests that pioglitazone can exert its antiatherogenic effect independently of its antidiabetic effect.
As for pressure ulcers care, prevention is the most important approach. However, pressure ulcers, might develop despite enough care, depending on each person's physical condition. As for the treatment of pressure ulcers, maintenance of a moderately moist environment (60-70%) is quite important. We propose the use of ointment to control the moisture of a pressure ulcer environment. One ointment base absorbs moisture, while another provides moisture. We have prepared a manual that allows the user to select the medicine according to the degree of moisture of the affected part. When the moisture cannot be regulated with one ointment, it can be adjusted by mixing two or more ointments. In choosing a drug for external use, it is important to pay attention not only to the effect of the main ingredient but also to the physicochemical properties of the ointment base that serves as vehicle for that active component.
As for pressure ulcers care, prevention is the most important approach. However, pressure ulcers, might develop despite enough care, depending on each person's physical condition. As for the treatment of pressure ulcers, maintenance of a moderately moist environment (60-70%) is quite important. We propose the use of ointment to control the moisture of a pressure ulcer environment. One ointment base absorbs moisture, while another provides moisture. We have prepared a manual that allows the user to select the medicine according to the degree of moisture of the affected part. When the moisture cannot be regulated with one ointment, it can be adjusted by mixing two or more ointments. In choosing a drug for external use, it is important to pay attention not only to the effect of the main ingredient but also to the physicochemical properties of the ointment base that serves as vehicle for that active component.