Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused mesenterial bed.

Anthocyanins, which are responsible for a variety of bright colors (including red, blue, and purple) in fruits, vegetables, and flowers, are consumed as dietary polyphenols. Anthocyanin-containing fruits are thought to decrease coronary heart disease and are used in anti-diabetic preparations. Diabetes is associated with a variety of cardiovascular complications that may be mediated by endothelial dysfunction, and so this study was designed mainly to characterize the influence of a synthesized anthocyanidin derivative (HK-008) over acetylcholine (ACh)-induced relaxation in mesenteric arterial beds isolated from rats. In a glucose-tolerance test in intact rats, HK-008 (30 mg/kg) reduced the glucose level as effectively as the same dose of glibenclamide. The aortic relaxation induced by pinacidil (an ATP-sensitive potassium channel opener) was greatly inhibited by glibenclamide (10 microM), and also significantly inhibited by HK-008 (10 microM). Interestingly, the ACh-induced relaxation in the perfused, preconstricted mesenteric arterial bed was significantly enhanced by HK-008 (10 microM), and this enhancement was significantly attenuated by indomethacin (10 microM). The ACh-induced mesenteric relaxation was impaired by an increase in oxidative stress, viz. superoxide-generating treatment [xanthine oxidase (XO; 0.1 U/ml) plus hypoxanthine (HX; 10 microM)]. However, this impairment was strongly suppressed by HK-008 (10 microM). These results suggest that HK-008 increases endothelium-induced relaxation by suppressing oxidative stress or modulating prostanoids signaling. This compound may therefore be useful against certain cardiovascular disorders.     

Effects of chronic administration of L-arginine on vasoactive responses induced by endothelin-1 and its plasma level in streptozotocin-induced diabetic rats.

To investigate the mechanism underlying increased endothelin-1 (ET-1) release in diabetic rats, we administered L-arginine chronically to streptozotocin (STZ)-induced diabetic rats. The plasma concentrations of glucose, ET-1 and NOx (NO2- + NO3-) were all significantly raised at 10 weeks after the STZ injection. Chronic administration of L-arginine resulted in a significantly higher plasma NOx concentration and a significantly lower plasma ET-1 level at 10 weeks compared with the untreated diabetic group. ET-1 induced a biphasic vasodilator/vasoconstrictor response in the perfused isolated mesenteric arterial beds from all groups. The vasodilatation was significantly greater in diabetic rats than in age-matched controls. Chronic oral L-arginine administration had no significant effect on the enhanced ET-1-induced vasodilatation seen in the untreated diabetic rats. The vasoconstrictions induced by ET-1 and methoxamine were significantly attenuated in STZ-diabetic rats. The attenuated vasoconstrictor response to ET-1, but not that to methoxamine, was further attenuated by chronic treatment with L-arginine. We conclude that since chronic L-arginine administration not only reduced the increase in plasma ET-1 levels but also further attenuated the ET-1-induced vasoconstriction without affecting the change in vasodilatation, chronic L-arginine administration could be valuable for the treatment of the symptoms of diabetic mellitus related to ET-1.     

TUMOR CELL PHAGOCYTOSIS AND CYTOTOXICITY OF LYMPHOBLASTOID CELLS FOLLOWING CONCANAVALIN A TREATMENT

Cell-to-cell interaction was investigated in various malignant tumor cells (human ovarial tumor, lung cancer, carcinoma of larynx and hamster melanoma cell) and in human lymphoblastoid cells (T-cell (MOLT-4 cell), thymoma cells and B-cells (Burkitt lymphoma cell)). Live lymphoblastoid cells did not adhere to the cell surfaces of tumor cells nor the lymphoblastoid cells were ingested by tumor cells wihout immunologic and specific treatment. Tumor cells as well as T-cells and B-cells had receptors to concanavalin A on their surfaces, and they showed marked cell binding of tumor cells and lymphoblastoid cells. Moreover, tumor cells that phagocytized lymphoblasts underwent marked cell destruction within 4 hours of cell binding. The cytolytic mechanism of the target tumor cell was probably related to contact with the lymphoblastoid cells and was increased by ingestive activity, and metabolic disturbance by lymphotoxin in tumor cells.     

Cell sheet engineering: recreating tissues without biodegradable scaffolds

While tissue engineering has long been thought to possess enormous potential, conventional applications using biodegradable scaffolds have limited the field's progress, demonstrating a need for new methods. We have previously developed cell sheet engineering using temperature-responsive culture dishes in order to avoid traditional tissue engineering approaches, and their related shortcomings. Using temperature-responsive dishes, cultured cells can be harvested as intact sheets by simple temperature changes, thereby avoiding the use of proteolytic enzymes. Cell sheet engineering therefore allows for tissue regeneration by either direct transplantation of cell sheets to host tissues or the creation of three-dimensional structures via the layering of individual cell sheets. By avoiding the use of any additional materials such as carrier substrates or scaffolds, the complications associated with traditional tissue engineering approaches such as host inflammatory responses to implanted polymer materials, can be avoided. Cell sheet engineering thus presents several significant advantages and can overcome many of the problems that have previously restricted tissue engineering with biodegradable scaffolds.     

Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle

Citrin is a mitochondrial aspartate glutamate carrier primarily expressed in the liver, heart, and kidney. We found that adult-onset type II citrullinemia is caused by mutations in the SLC25A13 gene that encodes for citrin. In this report, we describe the frequency of SLC25A13 mutations, the roles of citrin as a member of the urea cycle and as a member of the malate-aspartate shuttle, the relationship between its functions and symptoms of citrin deficiency, and therapeutic issues.     

Physical function and health-related quality of life of community-dwelling older adults with locomotive syndrome and pre-frailty

[Purpose] To consider the effective rehabilitation approaches for locomotive syndrome (LS) and pre-frailty, we examined the characteristics of physical function and health-related quality of life (HRQoL) in community-dwelling older adults. [Participants and Methods] Eighty-three individuals (age 71.8 ± 5.5 years, 29 males and 54 females) were divided into robust (R), LS, and locomotive syndrome with pre-frailty (LSP) groups. We compared the subscale and summary scores of the 36-Item Short-Form Health Survey (SF-36) as HRQoL indices. The grip strength, five-chair stand up test (SS-5), and normal walking speed were the physical function indices. [Results] The LS group had lower two-step scores and normal walking speed but there was no significant difference in the SF-36. The two-step score and 25-question geriatric locomotive function scale, SS-5, seven SF-36 subscales, and mental component summary (MCS) scores were lower in the LSP group. Compared to that of the LS group, the LSP group did not show significant difference in physical function but showed lower values in overall health, vitality, mental health, and MCS in the SF-36 subscales. [Conclusion] The subjective evaluation of one’s health was lower than that of the deterioration of physical function as a characteristic of the LSP.     

Mutational effects of γ-rays and carbon ion beams on Arabidopsis seedlings

To assess the mutational effects of radiation on vigorously proliferating plant tissue, the mutation spectrum was analyzed with Arabidopsis seedlings using the plasmid-rescue method. Transgenic plants containing the Escherichia coli rpsL gene were irradiated with γ-rays and carbon ion beams (320-MeV ¹²C⁶⁺), and mutations in the rpsL gene were analyzed. Mutant frequency increased significantly following irradiation by γ-rays, but not by 320-MeV ¹²C⁶⁺. Mutation spectra showed that both radiations increased the frequency of frameshifts and other mutations, including deletions and insertions, but only γ-rays increased the frequency of total base substitutions. These results suggest that the type of DNA lesions which cause base substitutions were less often induced by 320-MeV ¹²C⁶⁺ than by γ-rays in Arabidopsis seedlings. Furthermore, γ-rays never increased the frequencies of G:C to T:A or A:T to C:G transversions, which are caused by oxidized guanine; 320-MeV ¹²C⁶⁺, however, produced a slight increase in both transversions. Instead, γ-rays produced a significant increase in the frequency of G:C to A:T transitions. These results suggest that 8-oxoguanine has little effect on mutagenesis in Arabidopsis cells.