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.     

Variation analysis of β3-adrenergic receptor and melanocortin-4 receptor genes in childhood obesity

BACKGROUND: Decreased energy expenditure and increased food intake are principal causes for obesity. In the present study, genotypes of beta(3)-adrenergic receptor (beta(3)AR) and of melanocortin-4 receptor (MC4R), both of which are believed to have a close link to the cause of obesity, were analyzed and compared with phenotypes of childhood obesity. METHODS: Thirty-five obese children with moderate to severe obesity were enrolled. Direct sequencing of the MC4R coding region and pinpoint-polymerase chain reaction were used to detect genomic variation in the beta(3)AR gene using peripheral blood-derived DNA. RESULTS: Allele frequency of Trp64Arg variation in the beta(3)AR gene in the obese subjects was 0.16, which is comparable with that in the healthy general population in eastern Asia. Comparison of phenotypical characteristics did not show a significant difference between Trp/Trp and Trp/Arg subjects. It was notable that body height SD was significantly higher in the Trp/Trp than the Trp/Arg subjects (0.93 +/- 1.0 SD vs 0.07 +/- 1.3 SD, P= 0.03). Annual weight gains were far beyond a hypothetical fat gain in an Arg64 heterozygote with decreased energy consumption, suggesting increased food intake in childhood obesity. There was, however, no variation in the MC4R gene despite thorough sequencing of the entire coding region. CONCLUSIONS: The Trp64Arg variation in the beta(3)AR gene has no relationship to the degree or the incidence of childhood obesity. The majority of childhood obesity can be characterized as tall stature, more rapid weight gain than that expected by decreased energy expenditure. Further investigation is necessary in regard to the increased food intake as a major cause of childhood obesity.     

YF476 is a new potent and selective gastrin/cholecystokinin-B receptor antagonist in vitro and in vivo

Background : We newly synthesized YF476 ((R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2'-pyridyl)-1H-1,4-benzodiazepin-3-yl]-3-(3-methylamino-phenyl)urea) as a gastrin/cholecystokinin-B (CCK-B) receptor antagonist. We investigated the pharmacological profile of YF476 in vitro and in vivo .
Methods : We examined the binding properties of YF476 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, and the effect of YF476 on secretagogue-induced gastric acid secretion in rats and Heidenhain pouch dogs.
Results : YF476 replaced the specific binding of [¹²⁵I]CCK-8 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, with K _i values of 0.068, 0.62 and 0.19 n M , respectively. The affinity of YF476 for rat brain gastrin/CCK-B receptor was 4100-fold higher than that for rat pancreatic CCK-A receptor. In anaesthetized rats, intravenous YF476 inhibited pentagastrin-induced acid secretion with an ED ₅₀ value of 0.0086 μmol/kg, but did not affect histamine- and bethanechol-induced acid secretion at a dose of 10 μmol/kg. In Heidenhain pouch dogs, intravenous and oral YF476 inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner with ED ₅₀ values of 0.018 and 0.020 μmol/kg, respectively, but did not affect histamine-induced acid secretion.
Conclusion : These results suggest that YF476 is an extremely potent and highly selective gastrin/CCK-B receptor antagonist, and that the gastrin/CCK-B receptor is not involved in histamine- or bethanechol-induced gastric acid secretion in dogs or rats.     

GENOTYPES OF ALDH2 RELATED TO LIVER AND PULMONARY DISEASES AND OTHER GENETIC FACTORS RELATED TO ALCOHOLIC LIVER DISEASE

Genetic factors related to the development of alcoholic liverand pancreatic diseases (ALD and APD) and of alcohol-inducedasthma were analyzed. The development of ALD is geneticallycontrolled and is directly associated with the polymorphismsof the genes of acetaldehyde (Ac-CHO) and ethanol-metabolizingenzymes, aldehyde dehydrogenase-2 (ALDH2) and cytochrome P4502E1.The development of ALD and APD may also be genetically linkedwith the induction of gamma-glutamyl transferase (GTT) by alcohol.Alcohol-induced asthma is related to the genotypes of ALDH2and is caused by rapid elevation of blood Ac-CHO. ALDH1 playsa very important role in the oxidation of Ac CHO in blood.     

Magnetic Resonance Imaging Findings in Patients with Tarsal Tunnel Syndrome

Tarsal tunnel syndrome (TTS) is a common entrapment syndrome whose diagnosis can be difficult. We compared preoperative magnetic resonance imaging (MRI) and operative findings in 23 consecutive TTS patients (28 sides) whose mean age was 74.5 years. The 1.5T MRI sequence was 3D T2* fat suppression. We compared the MRI findings with surgical records and intraoperative videos to evaluate them. MRI- and surgical findings revealed that a ganglion was involved on one side (3.6%), and the other 27 sides were diagnosed with idiopathic TTS. MRI visualized the nerve compression point on 23 sides (82.1%) but failed to reveal details required for surgical planning. During surgery of the other five sides (17.9%), three involved varices, and on one side each, there was connective tissue entrapment or nerve compression due to small vascular branch strangulation. MRI studies were useful for nerve compression due to a mass lesion or idiopathic factors. Although MRI revealed the compression site, it failed to identify the specific involvement of varices and small vessel branches and the presence of connective tissue entrapment.     

Endoscopically proven case of rapid esophagogastric variceal progression and rupture as a result of portal hypertension with liver sarcoidosis

Sarcoidosis is a multi‐systemic disease of unknown etiology that results in the development of non‐caseating epithelioid granulomas. The liver is the third most frequently involved organ after the lymph nodes and the lungs. Most cases of liver sarcoidosis do not present with symptoms and involve minimal liver dysfunction, but some cases display progression to portal hypertension and liver cirrhosis, and finally to liver failure. The mechanism and the risk of progression in liver sarcoidosis are still unknown because of the diagnostic difficulty associated with this condition, and because follow‐up examinations can only be done in an invasive manner. Here, we present an informative case of liver sarcoidosis with rapid progression of esophagogastric varices. Four months prior to the definitive diagnosis, no signs of varices were observed on endoscopy, and developmentof esophagogastric varices, rapid progression, and eventual rupture occurred in a short period of time. A liver biopsy, carried out after endoscopic sclerotherapy, revealed that granulomas primarily affected the portal area without fibrotic and cirrhotic changes, which is considered a primary cause of portal hypertension and esophagogastric varices. Following the liver biopsy, the patient was given systemic steroids and is currently receiving outpatient care. Thus, we should consider the possibility that liver sarcoidosis, even in the absence of cirrhotic changes, can cause serious events such as esophagogastric variceal rupture following rapid progression as a result of portal hypertension.     

A survival case of acute mitral regurgitation and cardiogenic shock caused by subtotal occlusion of the first diagonal branch.

An 80-year-old woman was admitted with cardiogenic shock; she arrived in a deep coma with systolic blood pressure of 44 mmHg. An electrocardiogram showed ST elevation in I, aVL, V5 and V6, suggesting myocardial infarction in the lateral area of the left ventricle. A chest roentgenogram showed right pulmonary edema without cardiomegaly. Transthoracic and transesophageal echocardiograms revealed severe mitral regurgitation and a flailing anterior mitral valve leaflet, suggesting a ruptured papillary muscle. The patient was initially treated with high-dose dopamine, dobutamine and norepinephrine. Intraaortic balloon pumping was initiated after the patient's condition stabilized. She underwent emergency mitral valve replacement with a prosthetic valve. Complete rupture of the anterior papillary muscle was confirmed. Histological examination revealed necrosis of the anterior papillary muscle with inflammatory changes. She recovered uneventfully. Postoperative coronary angiography demonstrated subtotal occlusion of the first diagonal branch, and left ventriculography demonstrated akinesis of the lateral segment. This was a rare case in which subtotal occlusion of the first diagonal branch caused rupture of an anterior papillary muscle leading to severe mitral regurgitation.     

A rare congenital anomaly, bridge-like appendiceal fistula to the terminal ileum, demonstrated by MDCT

Although appendiceal anatomical anomalies are very rare, understanding of the anatomical details of these anomalies is important for surgery. In this case report, we present images from multi-detector row computed tomography (MDCT) and histological findings of a rare anatomical appendiceal anomaly originating from the cecum and opening into the terminal ileum like a bridge. These anatomical details were clearly depicted on MDCT with multi-planar reconstruction. MDCT demonstrated a communication between the appendix and terminal ileum. Histological analysis revealed that a normal mucosal layer was maintained from the appendix to the connected ileum, without any evidence of inflammatory or neoplastic changes, and only thickening of the muscular layer of the appendix was identified. Based on these histological findings, the appendix was considered to represent an anatomical anomaly rather than secondary fistula caused by inflammation or neoplasm, which has not yet been reported.     

Integration of Merged Delayed‐Enhanced Magnetic Resonance Imaging and Multidetector Computed Tomography for the Guidance of Ventricular Tachycardia Ablation: A Pilot Study

MDCT/MRI Fusion for the Guidance of VT Ablation . Background: Delayed enhancement (DE) MRI can assess the fibrotic substrate of scar‐related VT. MDCT has the advantage of inframillimetric spatial resolution and better 3D reconstructions. We sought to evaluate the feasibility and usefulness of integrating merged MDCT/MRI data in 3D‐mapping systems for structure–function assessment and multimodal guidance of VT mapping and ablation. Methods: Nine patients, including 3 ischemic cardiomyopathy (ICM), 3 nonischemic cardiomyopathy (NICM), 2 myocarditis, and 1 redo procedure for idiopathic VT, underwent MRI and MDCT before VT ablation. Merged MRI/MDCT data were integrated in 3D‐mapping systems and registered to high‐density endocardial and epicardial maps. Low‐voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were correlated to DE at MRI, and wall‐thinning (WT) at MDCT. Results: Endocardium and epicardium were mapped with 391 ± 388 and 1098 ± 734 points per map, respectively. Registration of MDCT allowed visualization of coronary arteries during epicardial mapping/ablation. In the idiopathic patient, integration of MRI data identified previously ablated regions. In ICM patients, both DE at MRI and WT at MDCT matched areas of low voltage (overlap 94 ± 6% and 79 ± 5%, respectively). In NICM patients, wall‐thinning areas matched areas of low voltage (overlap 63 ± 21%). In patients with myocarditis, subepicardial DE matched areas of epicardial low voltage (overlap 92 ± 12%). A total number of 266 LAVA sites were found in 7/9 patients. All LAVA sites were associated to structural substrate at imaging (90% inside, 100% within 18 mm). Conclusion: The integration of merged MDCT and DEMRI data is feasible and allows combining substrate assessment with high‐spatial resolution to better define structure–function relationship in scar‐related VT. (J Cardiovasc Electrophysiol, Vol. 24, pp. 419‐426, April 2013)