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.     

The effect of metronidazole on TPN-associated liver dysfunction in neonates

The effect of metronidazole (MNZ) on hepatic dysfunction associated with total parenteral nutrition (TPN) in neonates was investigated. Neonates receiving TPN for more than 2 weeks were divided into three groups. In group 1, TPN was given alone, in group 2, 25 mg/kg/d of MNZ was administered intravenously for the first 2 weeks of TPN, and in group 3, 50 mg/kg/d of MNZ was given for the first 3 weeks of TPN. Several parameters of liver function tests (LFTs) during the first 4 weeks of TPN were compared among these three groups. There was no significant difference of these parameters between group 1 and group 2. Although there was no significant difference of alkaline phosphatase, gamma-glutamyl transpeptidase, direct bilirubin, and total bile acid between groups 1 and 3, transaminase (glutamic oxaloacetic, glutamic pyruvic) of group 3 remained significantly lower than those of group 1. In conclusion, the administration of MNZ 50 mg/kg/d for 3 weeks, at least, prevented the elevation of transaminase during TPN in neonates, suggesting the possible involvement of intestinal anaerobic flora in the pathogenesis of TPN-associated liver dysfunction.     

Pharynx and oesophagus evaluation during the swallow using helical computerized tomography.

PURPOSE: Videofluorography (VF) and endoscopy are commonly used for dynamic imaging (DI) of pharyngeal swallowing but do not offer transverse plane (TP) information. The aim of the present study was to evaluate helical computerized tomography (HCT) to measure the DI capability pharyngeal swallowing in the TP. METHODS: The HCT scan technique used was a single-slice cine mode with scan times of 100 ms. All 15 subjects were studied supine during dry swallow, swallowing of barium sulphate jelly and 3, 10, 15 or 20 ml of a 40% barium sulphate solution. Nine subjects repeated the test twice at more than 1 week's interval to determine the test-retest reliability. RESULTS: Swallowing leads to closure of the vocal folds, pharyngeal constriction and narrowing of the piriform sinuses allowing jelly passage between the sinuses. Laryngeal elevation then occurs with the opening of the pharyngoesophageal segment (PES). Swallowing a bolus of 20 ml produced the maximum anteroposterior and transverse diameters as well as the maximum opening area of the PES. The test-retest intraclass correlation coefficients with liquid deglutition ranged from 0.86 to 0.98. CONCLUSIONS: This study shows that HCT enables visualization of TP of PES complementing VF or endoscopic swallowing studies.     

A case of granulocyte-colony stimulating factor producing gastric cancer]

We report a case of granulocyte-colony stimulating factor producing gastric cancer with multiple liver metastases. A 68-year-old woman who complained of epigastralgia visited our hospital. Upper gastrointestinal endoscopic examination revealed a type-2 gastric cancer. The laboratory data at admission indicated leukocytosis (35,900/microl) and a high level of serum granulocyte-colony stimulating factor (61 pg/mg). Granulocyte-colony stimulating factor producing gastric cancer was diagnosed by immunohistochemistry of biopsy specimen. Since we detected multiple liver metastases, chemotherapy was performed. Granulocyte-colony stimulating factor-producing gastric cancer is relatively rare and we summarize previous reports.     

Clinical studies on a newly devised amino acid solution for neonates

In 97 neonates receiving total parenteral nutrition in the postoperative period, clinical assessment was made for a newly devised amino acid solution (PF-I-III) from the standpoint of plasma amino acid profile and nutritional effect. These amino acid solutions prepared are characterized by the high concentration of branched-chain amino acids up to 40%, increased arginine and decreased glycine, phenylalanine and methionine as compared with commercially available solutions. In the PF group, each amino acid was kept within the range of standard value. Correlation between plasma amino acid profiles and the dose of each amino acid administered was obtained, from which minimum, standard, and maximum doses for each amino acid was determined. Based on these values, we proposed new formula for neonates which elicits no abnormal plasma amino acid pattern even when amino acids are administered at the dosage level of 1.5-2.5 g/kg/day.     

Detection of novel rearrangement of the JC virus gene in a case of progressive multifocal leukoencephalopathy with adult T-cell leukemia]

A 53-year-old man with adult T-cell leukemia (ATL) developed progressive left hemiparesis and left homonymous hemianopsia. Magnetic resonance imaging (MRI) one month later showed multiple high-intensity lesions in the white matter of both occipital lobes, with predominance in the right side. Detection of JCV genome with polymerase chain reaction in his cerebrospinal fluid subsequently confirmed the diagnosis of progressive multifocal leukoencephalopathy (PML). He was admitted to our hospital. The serum level of soluble interleukin-2 receptor in the patient increased, and both edema and new Gd-enhanced lesions were observed in the cortex of the occipital lobe. He was treated with systemic administrations of Pirarubicin. Cyclophosphamide, and Prednisolone. as well as intrathecal injection of Methotrexate and Cytarabine. Although these treatments temporarily alleviated the symptoms of PML. the ATL spread to the liver and kidney. He died of multiple organ failure. Analysis of his JCV genes revealed that there were three types of rearrangements in the regulatory domains of the JCV genes. All three types lacked the domain B. and two had duplicate domain A. This is the first report of the simultaneous detection of three different types of rearrangements in JCV genes in a single patient. It has been reported that white-matter lesions caused by typical PML are not enhanced in Gd-MRI. However. the lesions seen in this patient were enhanced in Gd-MRI. Such enhancement might be attributable to the modification of the lesions through the direct invasion of ATL cells to the central nervous system.     

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.