Non-invasive portography: a microbubble-induced three-dimensional sonogram for discriminating idiopathic portal hypertension from cirrhosis.

OBJECTIVES: The aim of this prospective study was to elucidate the efficacy of contrast-enhanced three-dimensional (3D) ultrasound with Sonazoid(®) (GF Healthcare, Oslo, Norway) as a non-invasive tool to discriminate idiopathic portal hypertension (IPH) from cirrhosis by demonstration of portal vein structure. METHODS: There were 16 patients: 11 with biopsy-proven cirrhosis and 5 with biopsy-proven IPH. Intrahepatic right portal vein images were taken by 3D ultrasound from 1 min after the injection of Sonazoid (0.0075 ml kg(-1)). Portal vein appearances were compared between 3D ultrasound and percutaneous transhepatic portography (PTP) by four independent reviewers. Sensitivity, specificity and area under the receiver operating characteristic curve (Az) of the images were used for the diagnosis of cirrhosis/IPH, and interimaging, inter-reviewer and interoperator agreement were examined. RESULTS: Sensitivity, specificity and Az of PTP for the diagnosis of cirrhosis/IPH were 63.6%/100%, 100% and 0.9 (0.71-1.0) by Reviewer I and 90.9%/100%, 100% and 1.0 by Reviewer III, respectively. Similarly, sensitivity, specificity and Az of 3D ultrasound for diagnosis of cirrhosis/IPH were 54.5%/80%, 100% and 0.96 (0.84-1.0) by Reviewer II and 72.7%/80%, 100% and 0.97 (0.9-1.0) by Reviewer IV, respectively. Diagnostic agreement between PTP and 3D ultrasound was good between Reviewers I and II (κ=0.793) and good between Reviewers III and IV (κ=0.732). Inter-reviewer agreement was good between Reviewers I and III for PTP diagnosis (κ=0.735), and good between Reviewers II and IV for 3D ultrasound diagnosis (κ=0.792). Interoperator agreement of diagnostic results was good (κ=0.740). CONCLUSION: Non-invasive visualisation of intrahepatic portal vein structure by contrast-enhanced 3D ultrasound with Sonazoid may have the potential to discriminate IPH from cirrhosis.

Withdrawal of pioglitazone in patients with type 2 diabetes mellitus.

BACKGROUND AND OBJECTIVE: The remodelling of the adipose tissue by pioglitazone may be associated with the sustained therapeutic effects. We studied the effects of withdrawal of pioglitazone after 3-month treatment on glucose, lipid and high-molecular weight (HMW) adiponectin levels as well as liver function in patients with type 2 diabetes mellitus. METHODS: Forty-nine Japanese patients with type 2 diabetes mellitus were randomly assigned into the withdrawal group after 3-month treatment with pioglitazone (15 or 30 mg daily) and the non-withdrawal group. RESULTS AND DISCUSSION: Three-month treatment with pioglitazone improved glycaemic control, homeostasis model assessment for insulin resistance (HOMA), dyslipidaemia and liver function tests in association with a marked increase in serum HMW adiponectin level. Three months later after the withdrawal of pioglitazone, however, fasting plasma glucose and HOMA increased, whereas serum HMW adiponectin decreased to the pretreatment levels. Dyslipidaemia also returned to the pretreatment level. On the other hand, liver enzymes at 3 months after the withdrawal remained lower after a mild rebound. In addition, the bone formation marker, serum bone-specific alkaline phosphatase, was significantly reduced by pioglitazone treatment in post-menopausal women. CONCLUSIONS: The present study suggests that 3-month treatment with pioglitazone has no sustained beneficial effects except in liver function tests in patients with type 2 diabetes mellitus.

Therapeutic effect of balloon-occluded retrograde transvenous obliteration for gastric varices in relation to haemodynamics in the short gastric vein.

The aim of this study was to elucidate the relationship between the therapeutic effect of balloon-occluded retrograde transvenous obliteration (B-RTO) and haemodynamic features in the short gastric vein (SGV) in patients with gastric fundal varices (GV). The subjects in this retrospective cohort study comprised 34 patients who had moderate- or large-grade GV with the SGV both on retrograde venography and Doppler ultrasound. The diameter, flow velocity and flow volume in the SGV measured by Doppler ultrasound before B-RTO with 1 h balloon occlusion were compared with the therapeutic effect. Embolisation of GV was achieved in 30/34 patients (88.2%): 27 by initial B-RTO and 3 by second B-RTO. Flow velocity and flow volume in the SGV before B-RTO were significantly lower in the 27 patients with a complete effect on initial B-RTO (7.19+/-2.44 cm s(-1), p = 0.0246; 189.52+/-167.66 ml min(-1), p = 0.002) than in the 7 patients with an incomplete effect (10.41+/-5.44 cm s(-1), 492.14+/-344.94 ml min(-1)). Neither endoscopy nor contrast-enhanced CT had recurrent findings of GV in the subject during the follow-up period (94-1440 days; mean, 487.2+/-480.5 days). In conclusion, haemodynamic evaluation of the SGV using Doppler ultrasound may be useful for the prediction of the therapeutic effect of B-RTO.

Reactive oxygen scavenging activity of matured whiskey and its active polyphenols.

The quality of whiskey is known to improve remarkably by its storage over many years. This process is commonly termed "maturing." In this process, polyphenols derived from lignin and tannin of the barrel have an important role in not only forming the matured flavor and taste but also contributing to the advance of clustering ethanol and water in whiskey. It is also likely that polyphenols generally possess reactive oxygen (RO) scavenging activity. The present study evaluated the RO scavenging activity (free-radical scavenging activity, H(2)O(2) reduction activity under peroxidase coculture, and H(2)O(2)scavenging activity) of 24 single malt whiskeys with a maturation age of 10 to 30 y produced in Japanese, Scotch (Islay), or Scotch (Speyside and Highland) regions. Single malt whiskey not only showed RO scavenging activity but there was also a positive correlation between this activity and the maturation age of whiskey exceeding the difference resulting from the manufacturing region. A nonvolatile fraction derived from the barrel was responsible for RO scavenging activity. In particular, the contents of ellagic and gallic acids and lyoniresinol, the main polyphenolic compounds in whiskey, increased with maturation age. For the free-radical scavenging activity per molecule, each compound was 1.68 to 3.14 times that of trolox (a water-soluble vitamin E). The activities of ellagic acid, gallic acid, and lyoniresinol in the whiskey (Yamazaki 18) were equivalent to that of 80.3, 31.2, and 11.1 ppm trolox, respectively. Accordingly, the total activity of these 3 compounds accounted for about 20% of the activity of the whiskey (630.7 ppm trolox).

Genetic variation of the norovirus GII-4 genotype associated with a large number of outbreaks in Chiba prefecture, Japan.

Between October and December, 2006, high activity of three genetically distinct norovirus GII-4 subtypes was observed in Chiba prefecture, Japan. One subtype was newly identified in this period and it was detected in 85% of outbreaks.

Application of percutaneous ultrasound-guided treatment for ultrasonically invisible hypervascular hepatocellular carcinoma using microbubble contrast agent.

AIM: To evaluate the efficacy of contrast-enhanced ultrasound for the localization of ultrasonically invisible hypervascular lesions in the liver to facilitate percutaneous ultrasound-guided treatment. MATERIALS AND METHODS: Forty patients with 47 ultrasonically invisible hypervascular lesions (5-20mm) diagnosed on contrast-enhanced computed tomography were enrolled in the retrospective study. Contrast-enhanced ultrasound (CEUS) with Levovist was performed to localize the lesions both in the early phase and liver-specific phase. Diagnosis of was confirmed by percutaneous needle biopsy where feasible, and on the basis of on treatment outcomes or changes in computed tomography findings in those not amenable to biopsy. RESULTS: Thirty-two lesions were diagnosed as hepatocellular carcinoma (HCC). Contrast-enhanced ultrasound localized hepatocellular carcinoma in 24/32 (75%) lesions, the mean diameter (15.1+/-4.9mm), as measured using computed tomography, being significantly larger than that of the remaining eight lesions (10.5+/-2.1mm). Ultrasound-guided treatment was performed in 19 of the 24 lesions, and transarterial chemoembolization (TACE) was applied for the other five lesions because of difficult percutaneous access. Five of the eight non-visualised lesions were treated by transarterial chemoembolization, and the other three by surgical resection. The beneficial effect of CEUS was significantly greater when the reason for poor initial visualisation was the coarse liver architecture (17/17) than when it was due to adverse location (seven of 15, p<0.005). Fifteen of the CT-detected hypervascular lesions were considered to represent false positives for HCC, based on their behaviour during follow-up. CONCLUSION: Contrast-enhanced ultrasound with Levovist facilitates the application of percutaneous ultrasound-guided treatment by improving localization of ultrasonically invisible hypervascular hepatocellular carcinomas in the liver.

Detection and sequence-based typing of human adenoviruses using sensitive universal primer sets for the hexon gene.

The universal primer sets for identification of human adenovirus (HAdV) targeting hexon gene were designed and applied to 121 clinical samples suspected of HAdV infection. The primer sets amplified at least 20 HAdV reference strains of six species. Of these clinical samples, 81 (66.9%) samples were positive for HAdV. They were classified into 11 serotypes belonging to 5 HAdV species (B-F). The primer sets described here are sensitive and reactive to the broad spectrum of HAdV and are useful for rapid diagnosis of various HAdV infections.

[Evaluation of endoscopic papillary balloon dilation (EPBD) using one-step catheter for removal of common bile duct stones].

We compared the results of EPBD in 18 patients using one-step catheter (one-step group) with those in 46 patients using usual two-step catheter (two-step group). The frequency of endoscopy and bile duct clearance were the equal in both groups. Pancreatitis occurred in only one patient of two-step group. Elevations of the amylase values were the equal in both groups. Amylase values after EPBD tended to decrease in 11 patients whose amylase values were above 500 IU/l before EPBD. Using one-step catheter in EPBD was useful for removing common bile duct stones easily and safety.

Endotoxin impairs biliary transport of sparfloxacin and its glucuronide in rats.

The effect of endotoxin on glucuronidation and hepatobiliary transport of quinolone antimicrobial agents was investigated in rats using sparfloxacin and p-nitrophenyl glucuronide as model drugs. The biliary clearance experiments were performed 24 h after a single intraperitoneal injection of endotoxin (1 mg/kg). Endotoxin significantly delayed the disappearance of sparfloxacin from plasma and increased plasma concentration of its glucuronide after intravenous injection of sparfloxacin (10 mg/kg). Significant decreases in the systemic clearance of sparfloxacin and the biliary clearance of sparfloxacin and the glucuronide were observed. Endotoxin had no effect on in vitro glucuronidation activity using p-nitrophenol as a substrate. When p-nitrophenyl glucuronide (8 mg/kg) was administered in endotoxin-pretreated rats, significant decreases in the systemic clearance, biliary clearance and renal clearance of p-nitrophenyl glucuronide were observed. These findings suggest that endotoxin decreases the biliary excretion of sparfloxacin and its glucuronide probably due to impairment of their hepatobiliary transport systems and renal handling.

Inhibitory effects of capsaicinoids on fatty acid desaturation in a rat liver cell line.

The inhibitory effects of such vanillylamides as capsaicin and nine capsaicinoids on fatty acid desaturation in liver cells were investigated by using the cultured rat liver cell line, BRL-3A. When capsaicin was added to the medium, it had a relatively strong inhibitory effect on delta6 desaturation and clear inhibitory effects on delta5 and C24delta16 desaturation (delta16 desaturation of C24-polyunsaturated fatty acids). Capsaicinoids with side carbon chain lengths of C10:0 and C12:0 expressed the maximum inhibitory effects of the nine capsaicinoids on fatty acid desaturation in the BRL-3A cells. The inhibitory effects of the capsaicinoids were not correlated with their pungency.

Staged coronary artery bypass grafting after percutaneous angioplasty for intracranial vascular stenosis.

OBJECTIVE: Cerebrovascular disease is commonly associated with coronary artery disease and is a major risk factor for cardiac surgery. Concomitant coronary artery bypass grafting and carotid endarterectomy may reduce the risk of stroke; however, this staged operation is effective only for extracranial lesions. The strategy for on-pump coronary artery bypass grafting for patients with intracranial vascular stenosis is still controversial. METHODS: The subjects were 157 consecutive candidates for coronary artery bypass grafting who underwent computed tomography and digital subtraction cerebral angiography preoperatively to check for cerebrovascular disease. Additional single-photon emission computed tomography was performed to evaluate cerebral ischemia, according to the neurologist's request. Patients with diffuse intracranial vascular stenosis impossible to treat with percutaneous transluminal angioplasty underwent off-pump coronary artery bypass grafting. Patients with a circumflex coronary artery lesion first underwent percutaneous transluminal angioplasty for cerebral vascular stenosis followed by secondary on-pump coronary artery bypass grafting. RESULTS: Three patients were selected for staged operations. Percutaneous transluminal angioplasty was performed for 4 intracranial stenotic lesions. All lesions were dilated successfully, and no complications developed during or after the procedure. All patients tolerated staged coronary artery bypass grafting and were extubated within 1 day without any mental disturbance. No further neurologic complication occurred, and computed tomography performed postoperatively revealed no significant changes. CONCLUSION: Staged on-pump coronary bypass after percutaneous transluminal angioplasty for cerebrovascular disease may reduce the risk of stroke during cardiopulmonary bypass, and it is useful especially in patients with intracranial cerebrovascular disease.

Competitive incorporation of arachidonic acid analogs by cultured rat keratinocytes.

Arachidonic acid (20:4 n-6) and its metabolic products, such as prostaglandins and leukotrienes, have been known to be associated with skin inflammatory reactions. However, the mechanism of the competitive incorporation of 20:4 n-6 into keratinocytes among polyunsaturated fatty acids (PUFAs) remains uncertain. To investigate the relationship between the molecular structure of PUFAs and the rate of incorporation of PUFAs into cells, a fetal rat skin keratinocyte (FRSK) cell line was used. The cells were incubated for 24 h with any two of the following arachidonic acid analogs: mead acid (20:3 n-9), dihomo-gamma-linolenic acid (20:3 n-6), 11,14,17-cis-eicosatrienoic acid (20:3 n-3), arachidonic acid (20:4 n-6), eicosapentaenoic acid (20:5 n-3) and 5,8,11,14-cis-nonadecatetraenoic acid (19:4 n-5), at the ratio of 1:0, 0.5:0.5, or 0:1; and their incorporation into lipid was measured by capillary gas-liquid chromatography. The experiments indicated that 20:3 n-6 was preferentially incorporated into phospholipids of FRSK rather than 20:3 n-9 or 20:3 n-3, and 19:4 n-5 as well as 20:4 n-6 was preferentially incorporated into total cellular lipid and phospholipids rather than 20:3 n-9 or 20:5 n-3. When two PUFAs were added simultaneously to the medium, 19:4 n-5 most effectively reduced the competitive incorporation of 20:4 n-6 into phospholipids. These results suggest that keratinocytes discriminate 20:4 n-6 from other arachidonic acid analogs by its double bond positions from the carboxyl group.

Ketoacidosis accompanied by epileptic seizures in a patient with diabetes mellitus and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).

We herein report a rare case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and diabetes mellitus with ketoacidosis. An 18-year-old female patient was diagnosed to have diabetes mellitus and insulin therapy was thereafter initiated. At 26 years of age, she was hospitalized for diabetic ketoacidosis, soon followed by a loss of consciousness, left-sided dysmetria, and ataxic speech. MELAS was diagnosed because of the presence of ragged red fibers in a muscle biopsy. At 33 years of age, she was admitted to our hospital because of ketoacidosis and partial status epilepticus. A blood gas examination revealed as follows; arterial pH, 6.88; bicarbonate, 2.1 mmol/l; base excess - 29.8 mmol/l. The serum level of glucose had also increased to 30 mmol/l. The serum levels of lactate and B-hydroxybutyrate were elevated to 11.4 mmol/l and 1,990 micromol/l, respectively. Ketoacidosis improved by fluid replacement and continuous intravenous insulin infusion. A brain MRI demonstrated hyperintensity areas on FLAIR images in the bilateral temporal lobes and the cerebellum. A proton MRS demonstrated the abnormal lactate accumulation in the bilateral temporal and occipital lobes. Since epileptic seizures are rare in patients with diabetic ketoacidosis, such seizures may indicate the existence of MELAS syndrome.

Terson syndrome caused by ventricular hemorrhage associated with moyamoya disease--case report.

A 24-year-old female presented with Terson syndrome secondary to bilateral ventricular hemorrhage as a complication of moyamoya disease. Ophthalmoscopy and magnetic resonance imaging clearly demonstrated vitreous hemorrhage in the left eye globe. Various visual symptoms are associated with moyamoya disease, almost all of which result from ischemic lesions in the visual cortex and optic pathways. In this case, the visual disturbance was caused by Terson syndrome secondary to ventricular hemorrhage. Close ophthalmological and radiological evaluation is mandatory even in patients with moyamoya disease and hemorrhagic manifestation located in the intracerebral, subarachnoid, or intraventricular space.

Ascorbic acid stimulation of production of a highly branched ,beta-1,3-glucan by Aureobasidium pullulans K-1--oxalic acid, a metabolite of ascorbic acid as the stimulating substance.

The production of a highly branched beta-1,3-glucan by Aureobasidium pullulans K-1 in Czapek's medium has been found to be stimulated by ascorbic acid. When the culture supernatant, after removal of polysaccharide from the culture filtrate by ethanol precipitation, was concentrated, then added to a new medium and this strain was cultured in the medium, the polysaccharide production was stimulated the same as when L-ascorbic acid was added to the medium. The stimulating substance was partially purified from the supernatant, and was found to be oxalic acid; 0.03% oxalic acid was the most effective concentration for the stimulation of polysaccharide production. The stimulating substance, oxalic acid, was proved to be derived from ascorbic acid added to a medium in an experiment using L-[1-14C]ascorbic acid. We suggest that oxalic acid generated from the metabolism of ascorbic acid in cells of Aureobasidium pullulans K-1 participated in the stimulation of the polysaccharide production by ascorbic acid.

Detection and characterization of modified nucleosides in serum and urine of uremic patients using capillary liquid chromatography-frit-fast atom bombardment mass spectrometry.

To determine RNA metabolism in uremia, capillary liquid chromatography-frit-fast atom bombardment mass spectrometry was employed for the characterization of ribonucleosides in serum and urine of uremic patients, and the profiles were compared with those of healthy subjects. We have characterized 20 nucleosides in serum and 23 nucleosides in urine from both healthy subjects and uremic patients; most of them were modified nucleosides derived from tRNA breakdown products. Four metabolites derived from allopurinol were detected as exogenous nucleosides in patients receiving allopurinol; these include allopurinol-1-riboside, oxipurinol-1-riboside, oxipurinol-7-riboside and a unknown oxipurinol riboside. The endogenous and exogenous ribonucleosides were retained at higher levels in uremic serum, and may play a contributory role as toxins responsible for clinical symptoms of uremia.

C19 odd-chain polyunsaturated fatty acids (PUfas) are metabolized to C21-PUfas in a rat liver cell line, and curcumin, gallic acid, and their related compounds inhibit their desaturation.

It was demonstrated that the rat liver cell line BRL-3A converted exogenous C19 odd chain-polyunsaturated fatty acids (PUFAs) into the corresponding C21- and C23-PUFAs as follows: 21:3n-8, 21:4n-8, 23:3n-8, and 23:4n-8 (from 19:3n-8); 21:4n-5, 21:5n-5, 23:4n-5, and 23:5n-5 (from 19:4n-5); 21:5n-2, 21:6n-2, 23:5n-2, and 23:6n-2 (from 19:5n-2). It presumed that these C19 PUFAs were converted through the mimic route to docosahexaenoic acid (22:6n-3) from eicosapentaenoic acid (20:5n-3). In addition, the characterization of the change of fatty acid composition of cellular lipids in rat liver cells were examined, using 19:4n-5 and several fatty acid desaturation inhibitors. Curcumin related compounds, curcumin, capsaicin, isoeugenol, 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one, and gallic acid esters with near five carbon numbered alcohol had great changes of fatty acid composition of cellular lipids based on inhibition of the A6 desaturation of C24-PUFAs in rat liver cells.

Probucol reduces lysophosphatidylcholines in low-density lipoprotein.

OBJECTIVES: Lysophosphatidylcholine (LPC) in low-density lipoprotein (LDL) comes into notice as an important atherogenic substance. METHODS: Since the effect of probucol, an antioxidative lipid-lowering drug, on LPC molecular species has not been elucidated, two LPC molecular species, stearoyl LPC (SLPC) and palmitoyl LPC (PLPC), were measured in LDL using high-pressure liquid chromatography. LDL was obtained from 11 hyperlipidemic patients, including 9 diabetic patients, in comparison with 11 age- and gender-matched controls. RESULTS AND CONCLUSION: Hyperlipidemic patients showed nearly twofold higher levels of SLPC and PLPC per gram of LDL protein than those of controls. All hyperlipidemic patients were treated with oral administration of 500 mg/day of probucol for 3 months. Both LPCs in LDL were significantly reduced to control levels and were increased again up to the pretreatment levels 4 weeks after cessation of the treatment. Therefore, probucol has a potent effect in reducing LPC and may contribute to decreasing the atherogenicity of LDL.

Novel nitric oxide and superoxide generation inhibitors, persenone A and B, from avocado fruit.

One known, (2R)-(12Z,15Z)-2-hydroxy-4-oxoheneicosa-12,15-dien+ ++-1-yl acetate (1), and two novel compounds, persenone A (2) and B (3), have been isolated from avocado fruit (Persea americana P. Mill), as inhibitors of superoxide (O(2)(-)) and nitric oxide (NO) generation in cell culture systems. They showed marked inhibitory activities toward NO generation induced by lipopolysaccharide in combination with interferon-gamma in mouse macrophage RAW 264.7 cells. Their inhibitory potencies of NO generation (1, IC(50) = 3.6; 2, IC(50) = 1.2; and 3, IC(50) = 3.5 microM) were comparable to or higher than that of a natural NO generation inhibitor, docosahexaenoic acid (DHA; IC(50) = 4.3 microM). Furthermore, compounds 1-3 and DHA markedly suppressed tumor promoter 12-O-tetradecanoylphorbol-13-acetate-induced O(2)(-) generation in differentiated human promyelocytic HL-60 cells (1, IC(50) = 33.7; 2, IC(50) = 1.4; 3, IC(50) = 1.8; and DHA, IC(50) = 10.3 microM). It is notable that they were found to be suppressors of both NO- and O(2)(-)-generating biochemical pathways but not to be radical scavengers. The results indicate that these compounds are unique antioxidants, preferentially suppressing radical generation, and thus may be promising as effective chemopreventive agent candidates in inflammation-associated carcinogenesis.

[The use of a modified vertical mandibular osteotomy for exposure of a distal cervical internal carotid artery].

We report herein the case of a 56-year-old woman who presented with repeated transient ischemic attacks (TIAs). Cerebral angiography revealed that the left redundant internal carotid artery (ICA) uncharacteristically curved medially. These findings were highly suggestive of an internal carotid artery aneurysm at the level between the first and second cervical vertebral bodies. The lesion was presumed to be difficult to access by the surgical procedure usually adopted in carotid endarterectomy. Thus, we decided to employ a modified vertical mandibular osteotomy. The operative view revealed that the lesion was atherosclerotic stenosis with ulceration, so carotid endarterectomy was indicated. This mandibular osteotomy not only provided us with wide, satisfactory exposure of the distal cervical internal carotid artery but also afforded good mandibular stability during the postoperative period.