Prevalence of hepatitis C virus infection in cases of B-cell lymphoma in Japan.

Aims: To determine the prevalence of hepatitis C virus (HCV) infection in B-cell lymphoma in Japan. HCV infection and type II (monoclonal IgM) cryoglobulinaemia (CG) may be involved in the pathogenesis of low-grade B-cell lymphoma (ML) in southern Europe.

Methods And Results: Forty-five (11.

Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine.

The goal of this study is to develop a novel sustained-release (SR) system for poorly water-soluble drugs by applying solid dispersion (SD) technique for improving the solubility. The developed SR system, disintegration-controlled matrix tablet (DCMT), consists of hydrogenated soybean oil (HSO) as wax and SD granules containing low-substituted hydroxypropylcellulose (L-HPC) as a disintegrant. In this study, nilvadipine (NiD) was chosen as a model compound.

Polyhistidine tract expansions in HOXA1 result in intranuclear aggregation and increased cell death.

HOXA1 gene is part of a cluster of homeotic selector genes that regulates the anteroposterior patterning of mammals during embryonic development. HOXA1 encodes two alternatively spliced mRNAs with two isoforms, A and B, the former contains the homeodomain and expressed in early embryonic development. HOXA1 contains a string of 10 histidine repeats.

Splenic large B-cell lymphoma in patients with hepatitis C virus infection.

Hepatitis virus infection, especially type C (hepatitis C virus [HCV]), has been suggested to be one of the important pathogenetic factors for low- and high-grade B-cell lymphoma, including splenic marginal zone lymphoma (SMZL), in southern Europe. Here, we analyzed the incidences of HCV and hepatitis B virus (HBV) infections, and the clinicopathologic features in 29 cases of splenic diffuse large B-cell lymphoma (DLBCL), 10 SMZL, 3 splenic mantle cell lymphoma, 1 hairy cell leukemia, 13 B-chronic lymphocytic leukemia, and 12 hepatosplenic T-cell and natural killer cell lymphoma. Fifteen (51.

Design of controlled-release morphine suppositories containing polyglycerol ester of fatty acid.

Controlled-release morphine suppositories were prepared by utilizing polyglycerol ester of fatty acid (PGEF). The addition of PGEF to fatty suppository base Witepsol H15 resulted in a decrease of morphine release rate from suppositories. Among PGEFs examined, decaglycerol heptabehenate (HB750) was the most effective additive for the controlled-release of morphine from fatty suppositories.

A novel marker for Purkinje cells, KIAA0864 protein. An analysis based on a monoclonal antibody HFB-16 in developing human cerebellum.

In the search for immunohistochemical markers of the developing human brain, a monoclonal antibody, HFB-16, was raised against homogenates from the cerebrum of a 15-gestational-week-old (GW) human fetus and screened on paraffin-embedded human embryonic brain specimens. This antibody was particularly useful as a marker for Purkinje cells in the developing human cerebellum. Positive immunoreactivities with HFB-16 first appeared in the Purkinje cell layer at 17 GW.

Skin permeation of propranolol from polymeric film containing terpene enhancers for transdermal use.

To develop the suitable film formulations of propranolol hydrochloride (PPL) containing enhancers for transdermal use, polymeric film formulations were prepared by employing ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP) as a film former, and dibutyl phthalate (DBP) as a plasticizer. Terpenes such as menthol and cineole, and propylene glycol (PG) were also employed as a chemical enhancer to improve the skin penetration of PPL. The film preparations were characterized in physical properties such as uniformity of drug content, thickness and moisture uptake capacity.

Enhancement of topical delivery of drugs via direct penetration by reducing blood flow rate in skin.

The purpose of this work was to investigate the effect of blood flow in the skin on the direct penetration of topically applied drugs into the muscular layer, and to show that the skin blood flow could also be one of the important factors determining the direct penetration of drugs to the muscular layer. In vivo percutaneous absorption study was performed for antipyrine, salicylic acid or diclofenac by using rats with tape-stripped skin. Phenylephrine, which is well known to reduce the local blood flow by vasoconstrictor action, was topically applied to decrease the local blood flow in the skin.

Analysis and prediction of absorption behavior for theophylline orally administered as powders based on gastrointestinal-transit-absorption (Gita) model.

Absorption behavior of theophylline, categorized into Class I of Biopharmaceutics Classification System, orally administered as powders in rats was analyzed and predicted by Gastrointestinal-Transit-Absorption (GITA) model, which was modified to describe GI-transit kinetics and dissolution of powders orally administered. First of all, GI-transit kinetics of glass beads was examined to describe the transit kinetics of powders through GI tract in rats. The results showed that the gastric emptying of glass beads was slower than that of solution, but that there was not much difference in the transit rate constants through the small intestine and cecum between glass beads and solution.

Pre-coating with serum albumin reduces receptor-mediated hepatic disposition of polystyrene nanosphere: implications for rational design of nanoparticles.

We evaluated the in vivo disposition characteristics of polystyrene nanospheres (NS) with the particle size of 50 nm (NS-50) pre-coated with human serum albumin (HSA) after intravenous administration in rats. HSA-coated NS-50 showed much longer blood-circulating property and the hepatic uptake clearance for HSA-coated NS-50 was about 1/5 of that for NS-50. In parallel with the results obtained in the in vivo study, liver perfusion experiments also showed that the hepatic disposition of HSA-coated NS-50 was much less than that of NS-50 in the presence of serum in the perfusate.

[Evaluation of multimodality therapy for synchronous liver metastases of gastric cancer].

We evaluated the significance of multimodality therapy for cases of liver metastases of gastric cancer. Accumulated survival rate and median survival time were analyzed for twenty cases of such gastric cancer. Survival rates of H1+H2 group and hepatic resection (HR) group were higher than that of H3 group and non-HR group.

[Effects of repeated intraperitoneal CDDP chemotherapy for the prevention of T3 and T4 gastric cancer].

We studied the significance of repeated intraperitoneal CDDP administration, as adjuvant chemotherapy, for the prevention of T3 and T4 gastric cancer. Fifty-two patients who had been operated as Curability B were divided into the following two groups, and the data on survival rate, median survival time and interval of "free of recurrence" were accumulated and analyzed. Group A consisted of nineteen patients treated with intraperitoneal CDDP administration and oral anticancer drugs.

[The significance of low-dose CDDP intraperitoneal administration for cases of peritoneal dissemination of gastric cancer].

We examined the significance of low-dose cisplatinum (CDDP) intraperitoneal administration for cases of peritoneal dissemination of gastric cancer. Sixty-eight cases of gastric cancer, diagnosed as P1 or CY1 in the gastrectomy operation that was carried out during the period between January 1994 and December 2001, were studied based on accumulated survival rate and mean survival time (MST). Ten milligram of CDDP was weekly administrated intraperitoneally through an infusion port.

Regulation of drug absorption from small intestine by enteric nervous system I: a poorly absorbable drug via passive diffusion.

To investigate the regulation of drug absorption from the small intestine by the enteric nervous system (ENS), the vascular-luminal perfusion study and the in-vitro transport study were performed by employing phenol red as a poorly absorbable model compound. The effect of ENS on the intestinal absorption of phenol red was examined by adding epinephrine, an adrenergic agonist, or bethanechol, a cholinergic agonist into the vascular perfusate in the vascular-luminal perfused rat small-intestine preparation. The viability of the perfused intestine was checked by the recovery of the vascular perfusate, net water flux and absorbability of antipyrine, a well absorbable drug, and it was confirmed that the function of the perfused small-intestine preparation was maintained for at least 1 hr.

Up-regulation of P-glycoprotein expression in small intestine under chronic serotonin-depleted conditions in rats.

To investigate the role of serotonin (5-HT), an important neurotransmitter and hormone/paracrine agent in the small intestine, in the transport activity of P-glycoprotein (P-gp), the intestinal transport of quinidine, a P-gp substrate, was examined in 5-HT-depleted rats prepared by intraperitoneal administration of p-chlorophenylalanine, a specific inhibitor of tryptophan hydroxylase in 5-HT biosynthesis. In the in vitro transport study, quinidine transport across rat jejunum was significantly enhanced in both the secretory and absorptive directions under 5-HT-depleted conditions, although the secretory transport was still predominant. The electrophysiological study suggested that the quinidine transport via passive diffusion was enhanced presumably through a paracellular route.

Metazoan and microbial models of Niemann-Pick Type C disease.

Niemann-Pick Type C (NP-C) disease compellingly provides insight into lipid transport and the association of this process with severe neuronal dysfunction. The two genes that define this syndrome, NPC1 and NPC2, are conserved throughout much of eukaryotic evolution, to the extent that the yeast and mammalian NPC1 genes are functionally interchangeable. We present here an evolutionary perspective of the genes defective in NP-C disease.

Pharmacokinetic analysis of factors determining elimination pathways for sulfate and glucuronide metabolites of xenobiotics. III: mechanisms for sinusoidal efflux of 4-methylumbelliferone sulfate.

1. To elucidate the mechanisms involved in the sinusoidal efflux of sulfate and glucuronide metabolites of 4-methylumbelliferone (4MU), isolated rat liver perfusion studies were performed under several conditions. 2.

Development of suppository formulation safely improving rectal absorption of rebamipide, a poorly absorbable drug, by utilizing sodium laurate and taurine.

To develop the safe formulation that can safely improve bioavailability of poorly absorbable drugs and that is practically available, we prepared the suppositories of rebamipide, a poorly soluble and poorly absorbable antiulcer drug, by employing the combinatorial use of sodium laurate (C12), an absorption enhancer, with taurine (Tau) or L-glutamine (L-Gln), an adjuvant exerting the cytoprotective action. Although the dissolution of rebamipide from fatty base (FB) suppository prepared using Witepsol H-15 was very slow, it was remarkably improved by the addition of C12 and L-Gln or Tau into the suppository. On the other hand, the dissolution of rebamipide from water-soluble base (WB) suppository prepared using polyethylene glycol was very rapid and the addition of adjuvants did not influence its dissolution so much.

N-octyl-beta-valienamine up-regulates activity of F213I mutant beta-glucosidase in cultured cells: a potential chemical chaperone therapy for Gaucher disease.

Gaucher disease (GD) is the most common form of sphingolipidosis and is caused by a defect of beta-glucosidase (beta-Glu). A carbohydrate mimic N-octyl-beta-valienamine (NOV) is an inhibitor of beta-Glu. When applied to cultured GD fibroblasts with F213I beta-Glu mutation, NOV increased the protein level of the mutant enzyme and up-regulated cellular enzyme activity.

Evaluation of sustained release suppositories prepared with fatty base including solid fats with high melting points.

To prepare the sustained release suppositories, solid fats such as polyglycerol ester of fatty acids (PGEFs) or beeswax were utilized with a fatty suppository base, Witepsol H15. PGEFs such as decaglycerol heptabehenate (HB750) and hexaglycerol pentastearate (PS500), and beeswax have relatively high melting points. The addition of PGEFs or beeswax to Witepsol H15 increased the apparent viscosity of suppository bases at 37 degrees C without any large change in the melting point of Witepsol H15.

Hepatic uptake of negatively charged particles in rats: possible involvement of serum proteins in recognition by scavenger receptor.

The mechanisms involved in the hepatic uptake of negatively charged carboxylated-polystyrene nanospheres with a size of 50 nm (CNS-50) were examined in rats. The liver perfusion experiments revealed that hepatic disposition of CNS-50 in the absence of serum could be partially ascribed to the direct recognition of the surface negative charge by scavenger receptors. On the other hand, the apparent negative charge of CNS-50 surface dramatically reduced in the presence of serum, because the adsorption of serum protein on their surface results in masking their intrinsic negative charge.

Increased NPC1 mRNA in skin fibroblasts from Niemann-Pick disease type C patients.

Niemann-Pick disease type C (NP-C) is an autosomal recessive lipid-storage disease that is characterized by progressive neurodegeneration and hepatosplenomegaly. Since identification of the NPC1 gene in 1997, a total of 120 disease-causing mutations have been reported. In this study, two novel mutations were identified, namely c.

Mutagenesis of the putative sterol-sensing domain of yeast Niemann Pick C-related protein reveals a primordial role in subcellular sphingolipid distribution.

Lipid movement between organelles is a critical component of eukaryotic membrane homeostasis. Niemann Pick type C (NP-C) disease is a fatal neurodegenerative disorder typified by lysosomal accumulation of cholesterol and sphingolipids. Expression of yeast NP-C-related gene 1 (NCR1), the orthologue of the human NP-C gene 1 (NPC1) defective in the disease, in Chinese hamster ovary NPC1 mutant cells suppressed lipid accumulation.

Chemical chaperone therapy for brain pathology in G(M1)-gangliosidosis.

We synthesized a galactose derivative, N-octyl-4-epi-beta-valienamine (NOEV), for a molecular therapy (chemical chaperone therapy) of a human neurogenetic disease, beta-galactosidosis (GM1-gangliosidosis and Morquio B disease). It is a potent inhibitor of lysosomal beta-galactosidase in vitro. Addition of NOEV in the culture medium restored mutant enzyme activity in cultured human or murine fibroblasts at low intracellular concentrations, resulting in a marked decrease of intracellular substrate storage.