Alleviation of dimethylnitrosamine-induced liver injury and fibrosis by betaine supplementation in rats.

Previous studies suggested that betaine intake might antagonize the induction of oxidative stress-mediated acute liver injury through regulation of the sulfur-amino acid metabolism. In this study we examined the protective effects of betaine on chronic liver injury and fibrosis induced by dimethylnitrosamine (DMN). Male rats were supplemented with betaine (1%, w/v) in drinking water from 2 weeks prior to the initiation of DMN treatment (10mg/(kg day), i.

Chemical constituents isolated from Polygala japonica leaves and their inhibitory effect on nitric oxide production in vitro.

A methanolic extract of dried leaves of Polygala japonica Houtt (Polygalaceae) significantly attenuated nitric oxide production in lipopolysaccharide-simulated BV2 microglia. Five anthraquinones chrysophanol (1), emodin (2), aloe-emodin (3), emodin 8-O-beta-D-glucopyranoside (4) and trihydroxy anthraquinone (5), and four flavonoids kaempferol (6), chrysoeriol (7), kaempferol 3-gentiobioside (8) and isorhamnetin (9) were isolated from the methanolic extract using bioactivity-guided fractionation. Among them, compounds 1-4, 6 and 7 showed significant inhibitory effect on lipopolysaccharide-induced nitric oxide production in BV2 microglia at the concentrations ranging from 1.

Calpain inhibitory flavonoids isolated from Orostachys japonicus.

The n-butanol (n-BuOH) fraction of Orostachys japonicus A. Berger (Crassulaceae) significantly inhibited calpain activity. Through the activity-guided isolation from the n-BuOH fraction, herbacetin 8-O-alpha-D-ribopyranoside (1), kaempferol (2), quercetin (3), afzelin (4), astragalin (5), isoquercetin (6) and quercitrin (7) were obtained.

Replica exchange simulations of transient encounter complexes in protein-protein association.

Recent paramagnetic relaxation enhancement (PRE) studies on several weakly interacting protein complexes have unequivocally demonstrated the existence of transient encounter complexes. Here, we present a computational method to study protein-protein binding by creating equilibrium ensembles that include both specific and nonspecific protein complexes. In a joint analysis of simulation and experiment we explore the physical nature and underlying physicochemical characteristics of encounter complexes involving three protein-protein interactions of the bacterial phosphotransferase system.

Antifibrotic activity of diterpenes from Biota orientalis leaves on hepatic stellate cells.

Antifibrotic effect of twelve diterpenes (1-12) from the 90% methanolic fraction of Biota orientalis leaves was evaluated employing HSC-T6 cells by assessing cell proliferation and morphological change. Among these diterpenes, totarol (8) and isopimara-8(14),15-dien-19-oic acid (9) dramatically reduced cell proliferation in dose-and time-dependent manner. Furthermore, treatment with these compounds resulted in the different pattern of morphological changes of HSC-T6 cells.

Stimulatory constituents of Eclipta prostrata on mouse osteoblast differentiation.

One flavonoid, diosmetin (1), and two isoflavonoids, 3'-hydroxybiochanin A (2) and 3'-O-methylorobol (3), were isolated from the methanol extract of Eclipta prostrata L. by a bioactivity-guided fractionation technique using primary cultures of mouse osteoblasts as an in vitro assay system. All three compounds significantly increased osteoblast differentiation as assessed by the alkaline phosphatase activity.

Charge fluctuations and correlation lengths in finite electrolytes.

Fluctuations of the charge Q_{Lambda} inside a subdomain Lambda embedded in an electrolyte contained in a finite cubical box of dimensions LxLxL with periodic boundary conditions are investigated. When Lambda is an LxL "slab" of width W , asymptotically exact expressions for the mean-square fluctuation Q_{Lambda};{2} are obtained in terms of the Lebowitz length xi_{L}(T,rho) and of the "true" or asymptotic screening/decay length xi_{Z,infinity}(T,rho) together, when the charge correlation decay is oscillatory, with the characteristic wavelength lambda_{Z}(T,rho) . In finite systems, the normalized charge fluctuations exhibit threefold scaling behavior in the ratios xi_{Z,infinity}W , Wlambda_{Z} , and WL .

Highly aligned ultrahigh density arrays of conducting polymer nanorods using block copolymer templates.

Ultrahigh density arrays of conducting polypyrrole (PPy) nanorods are fabricated directly on the indium-tin oxide coated glass by an electropolymerization within a porous diblock copolymer template. The nanorods are shown to have conductivity much higher than thin PPy films, due to the high degree of chain orientation, even though the separation distance for two neighboring PPy main chains is as small as 0.37 nm.

2R,3R-butanediol, a bacterial volatile produced by Pseudomonas chlororaphis O6, is involved in induction of systemic tolerance to drought in Arabidopsis thaliana.

Root colonization of plants with certain rhizobacteria, such as Pseudomonas chlororaphis O6, induces tolerance to biotic and abiotic stresses. Tolerance to drought was correlated with reduced water loss in P. chlororaphis O6-colonized plants and with stomatal closure, indicated by size of stomatal aperture and percentage of closed stomata.

Fixed, low-order controller design with time response specifications using non-convex optimization.

In this paper, we present a new algorithm for designing a fixed, low-order controller with time response specifications for a linear time invariant (LTI), single input single output (SISO) plant. For a two-parameter feedback configuration, the problem of finding a fixed or low-order controller to meet the desired time response specification is reduced to the least square estimation (LSE) in the sense of partial model matching (PMM), which minimizes a quadratic cost function. The closed-loop stability condition imposed on the controller parameters is formulated by the polynomial matrix inequality (PMI) constraint associated with the cost function.

Faster clearance of omeprazole in rats with acute renal failure induced by uranyl nitrate: contribution of increased expression of hepatic cytochrome P450 (CYP) 3A1 and intestinal CYP1A and 3A subfamilies.

It has been reported that omeprazole is mainly metabolized via hepatic cytochrome P450 (CYP) 1A1/2, CYP2D1 and CYP3A1/2 in male Sprague-Dawley rats, and the expression of hepatic CYP3A1 is increased in male Sprague-Dawley rats with acute renal failure induced by uranyl nitrate (U-ARF rats). Thus, the metabolism of omeprazole would be expected to increase in U-ARF rats. After intravenous administration of omeprazole (20 mgkg(-1)) to U-ARF rats, the area under the plasma concentration-time curve from time zero to infinity (AUC) was significantly reduced (371 vs 494 microg min mL(-1)), possibly due to the significantly faster non-renal clearance (56.

Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the central zinc-binding domain of the human Mcm10 DNA-replication factor.

The initiation of eukaryotic DNA replication requires the tightly controlled assembly of a set of replication factors. Mcm10 is a highly conserved nuclear protein that plays a key role in the initiation and elongation processes of DNA replication by providing a physical link between the Mcm2-7 complex and DNA polymerases. The central domain, which contains the CCCH zinc-binding motif, is most conserved within Mcm10 and binds to DNA and several proteins, including proliferative cell nuclear antigen.

Inhibitory constituents of lipopolysaccharide-induced nitric oxide production in BV2 microglia isolated from Amomum tsao-ko.

A methanolic extract of the fruits of AMOMUM TSAO-KO (Zingiberaceae) significantly attenuated nitric oxide production in lipopolysaccharide-simulated BV2 microglia. Two new bicyclic nonanes characterized as 6,7-dihydroxy-indan-4-carbaldehyde ( 1) and 6-hydroxy-indan-4-carbaldehyde ( 2) were isolated with the eleven known compounds 6,7-dihydroxy-3,7-dimethyloct-2-enoic acid ( 3), tsaokoin ( 4), isotsaokoin ( 5), 8-oxogeraniol ( 6), P-menth-1-ene-5,6-diol ( 7), 3alpha-hydroxycarvotagenone ( 8), tsaokoarylone ( 9), 1,7-bis(4-hydroxy-3-methoxyphenyl)-4,6-heptadien-3one ( 10), (+)-hannokinol ( 11), MESO-hannokinol ( 12) and hannokinin ( 13), from the fruits of A. TSAO-KO using bioactivity-guided fractionation.

Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice.

The cognitive-enhancing activities of E-harpagoside and 8-O-E-p-methoxycinnamoylharpagide (MCA-Hg) isolated from Scrophularia buergeriana were evaluated in scopolamine-induced amnesic mice by the Morris water maze and by passive avoidance tests. E-harpagoside and MCA-Hg significantly improved the impairment of reference memory induced by scopolamine in the Morris water maze test. The mean escape latency, the mean path length and swimming movement were also improved by both compounds.

Pharmacokinetic parameters of chlorzoxazone and its main metabolite, 6-hydroxychlorzoxazone, after intravenous and oral administration of chlorzoxazone to liver cirrhotic rats with diabetes mellitus.

Protein expression of the hepatic CYP2E1 has been reported to be increased in diabetic rats. This enzyme is the primary metabolizer of chlorzoxazone (CZX) to 6-hydroxychlorzoxazone (OH-CZX). Although patients with liver cirrhosis have a higher prevalence of diabetes mellitus, there have been no reported studies on the protein expression of CYP2E1 in rats induced to have liver cirrhosis and diabetes mellitus by injection of N-dimethylnitrosamine followed by streptozotocin [liver cirrhosis with diabetes mellitus (LCD) rats].

Relaxant Effect of Spermidine on Acethylcholine and High K-induced Gastric Contractions of Guinea-Pig.

In our previous study, we found that spermine and putrescine inhibited spontaneous and acetylcholine (ACh)-induced contractions of guinea-pig stomach via inhibition of L-type voltage-dependent calcium current (VDCC(L)). In this study, we also studied the effect of spermidine on mechanical contractions and calcium channel current (I(Ba)), and then compared its effects to those by spermine and putrescine. Spermidine inhibited spontaneous contraction of the gastric smooth muscle in a concentration-dependent manner (IC(50)=1.

Inactivation of pqq genes of Enterobacter intermedium 60-2G reduces antifungal activity and induction of systemic resistance.

Enterobacter intermedium 60-2G, a phosphate solubilizing bacterium, has the ability to induce systemic resistance in plants against soft rot pathogen Erwinia carotovora. Glucose dehydrogenase, an enzyme that utilizes pyrroloquinoline quinone (PQQ) as a cofactor, is required for the synthesis of gluconic acid by E. intermedium 60-2G.

A pinusolide derivative, 15-methoxypinusolidic acid from Biota orientalis inhibits inducible nitric oxide synthase in microglial cells: implication for a potential anti-inflammatory effect.

The inhibitory effect of 15-methoxypinusolidic acid (15-MPA) isolated from Biota orientalis (Cupressaceae) on lipopolysaccharide (LPS)-induced inflammation in microglial BV2 cells was investigated. 15-MPA significantly reduced the expression of inducible nitric oxide synthase (iNOS), the activity of iNOS, and the production of nitric oxide (NO) in LPS-stimulated BV2 cells. In addition, 15-MPA significantly suppressed the expressions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and cyclooxygenase (COX)-2.

A case of combined hepatocellular-cholangiocarcinoma with underlying schistosomiasis.

Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer showing features of both hepatocellular and biliary epithelial differentiation. We report here on a case with collision tumor, which apparently was the coincidental occurrence of both hepatocellular carcinoma and cholangiocarcinoma underlying schistosomiasis. A 39-year-old-Philippine female was transferred to our hospital for evaluation of a liver mass that was found on ultrasonography at a local hospital.

Time-dependent effects of Klebsiella pneumoniae endotoxin (KPLPS) on the pharmacokinetics of theophylline in rats: return of the parameters in 96-hour KPLPS rats to the control levels.

It has been reported that theophylline is primarily metabolized via hepatic CYP1A1/2, 2B1/2, and 3A1/2, and 1,3-dimethyluric acid (1,3-DMU) is primarily formed via CYP1A1/2 in rats. Compared with control rats, the expression of CYP1A subfamily, 2B1/2, and 3A subfamily significantly decreased 24 h (24-h KPLPS rats) after intravenous administration of lipopolysaccharide derived from Klebsiella pneumoniae (KPLPS) to rats but returned to that in control rats after 96 h (96-h KPLPS rats). After intravenous or oral administration of theophylline to 24-h KPLPS rats, the values for the total area under the plasma concentration-time curve from time zero to time infinity of theophylline and 1,3-DMU became significantly greater (46.

Comparison of the effects of buthioninesulfoximine and phorone on the metabolism of sulfur-containing amino acids in rat liver.

Alterations in hepatic transsulfuration reactions were determined in rats treated with a glutathione-depleting agent. A dose of l-buthionine-(S,R)-sulfoximine decreased hepatic methionine, cysteine, S-adenosylmethionine, and glutathione levels rapidly. Methionine adenosyltransferase and gamma-glutamylcysteine lygase activities were decreased transiently, but significantly.

Alleviation of acute ethanol-induced liver injury and impaired metabolomics of S-containing substances by betaine supplementation.

Oxidative stress is suggested to play a key role in the development of alcoholic liver injury. We investigated the induction of oxidative damage in association with changes in hepatic concentrations of sulfur-containing substances in mice challenged with binge-like ethanol administration. Also the protective effect of dietary betaine against ethanol-induced liver injury was determined.

Neuroprotective limonoids of root bark of Dictamnus dasycarpus.

A methanolic extract of Dictamnus dasycarpus root bark afforded four new degraded limonoids, 9alpha-hydroxyfraxinellone-9- O-beta- d-glucoside ( 1), dictamnusine ( 2), dictamdiol A ( 3), and dictamdiol B ( 4), together with eight known compounds, dictamdiol ( 5), fraxinellone ( 6), fraxinellonone ( 7), 9beta-hydroxyfraxinellone ( 8), calodendrolide ( 9), obacunone ( 10), limonin ( 11), and rutaevin ( 12). Compounds, 2, 3, 6, 9, 10, and 11 showed significant neuroprotective activity against glutamate-induced neurotoxicity in primary cultures of rat cortical cells at a concentration of 0.1 microM.

[Clinical review of gastrointestinal carcinoid tumor and analysis of the factors predicting metastasis].

Background/aims: Carcinoid tumors are submucosal tumors with metastatic potential. We tried to determine the clinical course of gastrointestinal (GI) carcinoid tumors and find the factors predicting metastasis.

Methods: We reviewed the clinical records of 81 cases with GI carcinoid tumors.

Effects of Escherichia coli lipopolysaccharide on telithromycin pharmacokinetics in rats: inhibition of metabolism via CYP3A.

It has been reported that telithromycin is metabolized primarily via hepatic microsomal cytochrome P450 (CYP) 3A1/2 in rats and that the expression of hepatic and intestinal CYP3A decreases in rats pretreated with Escherichia coli lipopolysaccharide (ECLPS rats; an animal model of inflammation). Thus, it is possible that the area under the plasma concentration-time curve from 0 h to infinity (AUC 0-infinity) of intravenous and oral telithromycin is greater for ECLPS rats than for the controls. To assess this, the pharmacokinetic parameters of telithromycin were compared after intravenous and oral administration (50 mg/kg).