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.     

A new pedicled seromuscular flap technique for high-risk intestinal anastomoses

A new method for protecting intestinal anastomoses in patients at high risk of anastomotic dehiscence or fistula formation is described herein. This method involves raising a seromuscular flap on a pedicle from the stump of the intestine to be anastomosed. The anastomosis is performed, then covered with the seromuscular flap.     

Classification of Diabetes Mellitus by Studies of C-Peptide Secretory Capacity

Residual pancreatic B-cell function was investigated in children with diabetes mellitus in whom classification of the type of disease was difficult at the first visit. Intravenous glucagon tests were performed at the first visit and subsequently, the C-peptide responses compared. Based on our data on a limited number of patients, we propose C-peptide concentrations of 3.0 to 3.5 ng/ml at the peak or at 6 min after injection of glucagon, as the critical level which distinguishes non-insulin dependent from insulin-dependent diabetes mellitus. However, the degree of obesity, clinical stage and other factors also need to be considered in the classification of diabetes mellitus.     

Seasonal variation in the content of a febrifugine and isofebrifugine alkaloid mixture in aerial parts of <Emphasis Type="Italic">Hydrangea macrophylla</Emphasis> var. <Emphasis Type="Italic">Otaksa</Emphasis>, with special reference to its antimalarial activity

Febrifugine and isofebrifugine alkaloid mixtures extracted from the leaves and buds of Hydrangea macrophylla var. Otaksa, collected during different months, in Japan, were quantified using high-performance liquid chromatography. Leaves collected during the flowering season, namely from June to August, contained 0.16–0.31 mg/g of the alkaloid mixture, whereas those collected from September to December had less than 0.03 mg/g of the mixture. However, extracts of buds harvested from October to February contained a consistently larger amount (more than 0.49 mg/g) of the alkaloids. Hot-water extracts from the leaves and buds collected during different seasons were evaluated for antimalarial activity against Plasmodium yoelii 17XL in mice. The extract of leaves collected in August demonstrated high antimalarial activity, and all mice that received the extract survived the infection. In contrast, the extract of leaves collected in December showed little activity. The extract of buds collected in December cleared parasites, but with subsequent mortality to mouse. The present results show that the amount of antimalarial agent—febrifugine and isofebrifugine mixture—in H. macrophylla var. Otaksa is both part- and season-dependent, suggesting that the choice of plant parts and their harvesting season are important factors worth considering in the pharmacological use of medicinal plants.     

Fractalkine and inflammatory diseases]

The migration of leukocytes into inflamed peripheral tissues and lymphoid organs involves a cascade of molecular events finely regulated by cell adhesion molecules and chemokines. Fractalkine/CX3CL1 is a membrane-bound chemokine that functions not only as a chemoattractant but also as an adhesion molecule, and is expressed on endothelial cells activated by proinflammatory cytokines. The fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes including NK cells and cytotoxic effector T cells (T(CE)), mature monocytes/macrophages, and mucosal dendritic cells, all of which play important roles in elimination of pathogens and cancer cells. Recently, accumulating evidence in both clinical studies and animal disease models has shown that fractalkine is also involved in the pathogenesis of various chronic inflammatory diseases, such as rheumatoid arthritis and atherosclerosis. This article reviews the unique functions of fractalkine and its pathophysiological roles in various clinical conditions.     

Scintigraphic detection of recurrence of medullary thyroid cancer

A case of recurrent medullary thyroid cancer (MTC) was evaluated with¹²³I-MIBG,^99mTc(V)-dimercaptosuccinic acid (DMSA), and²⁰¹Tl scintigraphy. This patient had been operated on for MTC in the right thyroid. Recently a left neck mass was noticed, and was suspected of being a. recurrence of MTC based on increased plasma calcitonin (CT) and carcinoembryonic antigen (CEA). He was operated on for the neck mass which revealed MTC, and papillary thyroid cancer was incidentally found in the left thyroid, but the CT and CEA levels remained high, and remaining MTC tumor was suspected. But the location of the tumor was unknown. Although^99mTc(V)-DMSA scintigraphy is generally believed to be superior in sensitivity to¹²³I-MIBG scintigraphy, it did not demonstrate the tumor site but²⁰¹Tl and¹²³I-MIBG did. Furthermore,¹²³I-MEBG scintigraphy has greater specificity for tumors which arise in the neural crest. Judging from the results of this case and cases reported in the literatures, both¹²³I-MIBG and^99mTc(V)-DMSA should be performed in the detection of recurrent MTC.     

Prevention of Restenosis after Coronary Angioplasty with Low-Density Lipoprotein Apheresis

Abstract: A prospective study was performed to determine whether low-density lipoprotein (LDL) apheresis, when performed only immediately before and after percutaneous transluminal coronary angioplasty (PTCA), is effective in preventing restenosis of coronary artery lesions following PTCA. Thirty-six patients with coronary heart disease (CHD) and hypercholesterolemia were divided into 2 groups. The 9 patients in the LDL group underwent LDL-apheresis 1 day before and 5 days after PTCA while the 27 patients of the control group underwent PTCA but did not undergo LDL-apheresis. Follow-up coronary angiography (CAG) was performed 4 months after PTCA. The rate of restenosis of coronary artery lesions was significantly lower in the LDL group (0%) than in the control group (30%). These findings suggest that LDL-apheresis, when performed before and after PTCA, is effective in preventing restenosis of coronary artery lesions in patients with CHD and hypercholesterolemia.     

Significance of the hepatic mitochondrial redox state in the development of posttraumatic jaundice

The effect of the hepatic energy status on the development of posttraumatic jaundice (PTJ) was studied to clarify the mechanism of PTJ. Fifty-four patients with severe torso injury who were expected to develop PTJ on admission with an average Injury Severity Score of 27 were selected for this study. They were retrospectively divided into three groups according to their maximum bilirubin concentration by day 10: group H, 12 patients with marked elevation of serum bilirubin (>8 g/dl); group L, 23 with mild bilirubinemia (2–8 g/dl); and group N, 19 with no bilirubinemia (<2 g/dl). Group H patients, in whom trauma-related shock was severe and prolonged, developed severe hyperbilirubinemia, and their arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state and is closely correlated to its energy production, was significantly lower throughout the first week. In contrast, the AKBR increased to an above normal level, indicating enhanced energy production in groups N and L. The serum direct/total bilirubin was also higher in group H. The abnormal hepatic energy metabolism is considered to have reduced the excretion of conjugated bilirubin from the hepatocytes into the bile canaliculi, which is a process that has to proceed against the bilirubin concentration gradient. The subsequent diffusion of the accumulated water-soluble conjugated bilirubin in hepatocytes into the blood is thus considered to be one of the causes of PTJ.     

AUGMENTATION OF ANGIOTENSIN II RELEASE FROM ISOLATED MESENTERIC ARTERIES OF WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS FOLLOWING NEPHRECTOMY

1. We previously reported that angiotensin II release from the mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) increased in a time-dependent manner as a result of the isolation of the arteries and perfusion. This phenomenon appeared to be due to the withdrawal of circulating angiotensin II (AII). 2. The purpose of the present study was to test the hypothesis that vascular AII generation may be negatively regulated by circulating AII in WKY and SHR, and to clarify the role of this vascular angiotensin II in the sustained hypertension of SHR following nephrectomy. 3. The mesenteric arteries from kidney-intact and nephrectomized WKY and SHR were perfused and the amount of AII released into the perfusate was measured. The effects of the angiotensin converting enzyme inhibitor, captopril, and the effects of supplementation of renal renin and circulating angiotensins to nephrectomized rats, by blood exchange between kidney-intact and nephrectomized rats, on AII release were examined to clarify the pathway of vascular AII generation after nephrectomy. 4. Nephrectomy caused augmentation of vascular AII release both in WKY and SHR in spite of the abolishment of circulating renin. Captopril reduced this enhanced release of AII, but blood exchange did not affect it. There was no significant difference in these responses between WKY and SHR. 5. These results suggest that WKY and SHR have in common a potent pathway for production of vascular AII in response to the withdrawal of circulating AII, although this pathway is not responsible for the sustained hypertension of SHR after nephrectomy. The precise pathophysiological role of this pathway remains to be elucidated.