Inhibitory effects of Japanese apricot (Prunus mume Siebold et Zucc.; Ume) on Helicobacter pylori-related chronic gastritis.

OBJECTIVES: We investigated the correlation between Japanese apricot (JA) intake and Helicobacter pylori-related chronic atrophic gastritis (CAG). METHODS: A questionnaire was administered and serum anti-H. pylori IgG antibodies measured in 1358 asymptomatic adults. The subjects were divided into high-intake and low-intake groups. Histological and serological evaluation of H. pylori-related CAG was performed in 68 non-elderly volunteers. RESULTS: The H. pylori-negative rate did not differ significantly between the high-intake and low-intake groups. Mean antibody titers were lower in the high-intake group, but the difference was not significant. There was no significant difference in the rate of H. pylori infection on the basis of JA intake when subjects were stratified by age. Among H. pylori-positive non-elderly subjects, antibody titers were significantly lower in the high-intake group (P=0.041). Endoscopic tissue biopsy from the 68 volunteers showed less H. pylori bacterial load and mononuclear infiltration irrespective of gastric site in the high-intake group. In the high-intake group, antral neutrophil infiltration was significantly less pronounced and corporal atrophy was less extensive. Serological evaluation using serum PG levels also confirmed these histopathological data. CONCLUSIONS: Our findings strongly indicate a preventive effect of JA intake on CAG by inhibiting H. pylori infection and reducing active mucosal inflammation.

Effect of calcium supplementation on bone dynamics of the maxilla, mandible and proximal tibia in experimental osteoporosis.

The effect of calcium supplementation on the bone dynamics in the hard palate of the molar region (maxilla), mandible and proximal tibia in experimental osteoporotic rats was examined. Ninety ovariectomized (OVX) and 45 sham-OVX Wistar female rats were used in this study. All the rats received surgical operation at 6 weeks of age. Ovariectomized rats were fed on a low calcium diet (0.02%) for 12 weeks post-operation, and then randomly divided into the two following groups. One group was fed on high calcium diet (2.30%) (OVX-HCa) and the other group was remained on the low calcium diet (OVX-LCa). Sham-OVX rats were fed on regular calcium diet (1.15%) during the experimental period (Sham-OVX). Histomorphological analysis was carried out from 12 to 32 weeks post-operation. On undecalcified thin section, bone volume, eroded surface, osteoid surface and bone formation rate were calculated for cortical bone of the maxilla, and for cancellous bone of the mandible and proximal tibia. In the OVX-LCa group, compared with the Sham-OVX group, decrease of the bone volume and increase of the bone resorption and formation parameters were detected throughout the observation periods. In the OVX-HCa group, compared with the OVX-LCa group, increase of the bone volume and temporarily increased parameters of bone formation at 1 week after feeding on high calcium diet were observed in the maxilla, but these changes were not observed in the mandible and proximal tibia. Moreover, the bone resorption and formation parameters in the maxilla, mandible and proximal tibia in the OVX-HCa group became equivalent to the Sham-OVX levels with the passage of time.

Diffusion-weighted MR findings in a reversible case of acute Wernicke encephalopathy.

We report a case of acute Wernicke encephalopathy (WE) in which apparent diffusion coefficient maps showed areas of increased diffusion in the bilateral medial thalami that corresponded to the hyperintense lesions on T2-weighted imaging. The hyperintense lesions on T2-weighted imaging disappeared with full recovery from symptoms. These findings suggest that the hyperintense lesions of the acute changes of WE include reversible vasogenic edema and are not caused by acute ischemia.

Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6.

Herbs as alternative cancer therapies have attracted a great deal of recent attention due to their low toxicity and costs. In this study, the antitumor activity and anticachectic effect of Coptidis rhizoma, an anti-inflammatory herb, were investigated in nude mice carrying a human esophageal cancer cell line YES-2, which constitutively secretes interleukin-6 (IL-6) and induces cachexia when injected into these mice. In this study, in vivo growth of YES-2 cells was not affected by an oral supplement containing the extract powder of C. rhizoma at a final concentration of 1% (CR supplement). However, in comparison with normal diet, CR supplement significantly attenuated weight loss of tumor-bearing mice without a change in food or water intake. Tumor IL-6 levels were significantly lower in mice treated with CR supplement than in control mice (P<0.001). Serum IL-6 was detectable in four (50%) of eight control mice; IL-6 was not detected in mice treated with CR supplement. We also confirmed that berberine (8-32 microM), a major component of C. rhizoma, dose-dependently inhibited secretion of IL-6 by YES-2 cells in vitro. Moreover, reverse transcription-PCR assay showed that treatment of YES-2 cells with berberine (8-32 microM) for 24 h reduced IL-6 mRNA expression. Our results suggest that C. rhizoma may have an anticachectic effect on esophageal cancer and an effect is associated with the ability of berberine to down-regulate tumor IL-6 production.

Porous apatite-wollastonite glass-ceramic as an intramedullary plug.

We evaluated the efficacy and biocompatibility of porous apatite-wollastonite glass ceramic (AW-GC) as an intramedullary plug in total hip replacement (THR) for up to two years in 22 adult beagle dogs. Cylindrical porous AW-GC rods (70% porosity, mean pore size 200 microm) were prepared. Four dogs were killed at 1, 3, 6 and 12 months each and six at 24 months after implantation. Radiological evaluation confirmed the efficacy of porous AW-CG as an intramedullary plug. Histological evaluation showed osteoconduction at one month and resorption of the porous AW-GC, which was replaced by newly-formed bone, at 24 months. Our findings indicate that porous AW-GC can be used clinically as an intramedullary plug in THR.

Development of artificial articular cartilage.

Attempts have been made to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which the lubrication and load-bearing mechanisms of natural and artificial joints are compared. Polyvinyl alcohol hydrogel (PVA-H), 'a rubber-like gel', was investigated as an artificial articular cartilage and the mechanical properties of this gel were improved through a new synthetic process. In this article the biocompatibility and various mechanical properties of the new improved PVA-H is reported from the perspective of its usefulness as an artificial articular cartilage. As regards lubrication, the changes in thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading were measured and it was found that PVA-H had a thicker fluid film under higher pressures than polyethylene (PE) did. The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times that of PE. Histological studies of the articular cartilage and synovial membranes around PVA-H implanted for 8-52 weeks showed neither inflammation nor degenerative changes. The artificial articular cartilage made from PVA-H could be attached to the underlying bone using a composite osteochondral device made from titanium fibre mesh. In the second phase of this work, the damage to the tibial articular surface after replacement of the femoral surface in dogs was studied. Pairs of implants made of alumina, titanium or PVA-H on titanium fibre mesh were inserted into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. The clinical implications of the possible use of this material in articular resurfacing and joint replacement are discussed.

Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines.

Our previous study demonstrated that the herbal medicine, Oren-to, had antitumor effects on esophageal cancer cells (ECCs) in vitro. The purpose of this study was to examine which of the seven constituents of Oren-to had antitumor effects on esophageal cancer cells. MTT assay showed that, of the seven constituents, only the aqueous extract of Coptidis Rhizoma had potent inhibitory effect on the proliferation of two types of ECC lines, YES-3 and YES-4. In addition, the proliferation of all six types of ECC lines (YES-1 to YES-6) was inhibited in a dose-dependent manner (P<0.001 for all), when co-cultured at each concentration of Coptidis Rhizoma for 72 h. The ID50 of Coptidis Rhizoma for YES-1 to YES-6 was 2.2 microg/ml, 3.0 microg/ml, 0.25 microg/ml, 2.8 microg/ml, 2.5 microg/ml, and 0.5 microg/ml, respectively, berberine, one of protoberberine components of Coptidis Rhizoma, showed potent antitumor effects on all six types of ECC lines as well as Coptidis Rhizoma. In addition, the ID50 of berberine showed a positive correlation with that of Coptidis Rhizoma in six types of ECC lines examined (r2 = 0.763, P = 0.023). Cell cycle analysis of Coptidis Rhizoma-treated cancer cells showed the accumulation of cells in the G0/G1 phase and relative decrease of the S phase. These results support the possibility that the use of Coptidis Rhizoma containing abundant berberine may be useful as one of alternative therapies for esophageal cancers.

The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma.

Recently, nm23-H1, an anti-metastasis gene, has been reported to correlate with sensitivity to chemotherapeutic agents including cisplatin in human breast and ovarian carcinoma cells. The aim of this study was to evaluate a role for nm23-H1 in responsiveness to cisplatin-based chemotherapy in patients with oesophageal squamous cell carcinoma (OSCC). The expression of nm23-H1 protein was examined immunohistochemically in 32 eligible patients with OSCC who underwent adjuvant chemotherapy with cisplatin, etoposide, and 5-fluorouracil after tumour resection. Fifteen (46.9%) of 32 patients were positive for nm23-H1 staining and 17 (53.1%) were negative. Both disease-free survival and overall survival rates of nm23-H1-negative patients were significantly shorter than in nm23-H1-positive patients (P < 0.01 for both). There was no significant difference in clinicopathologic characteristics between nm23-H1-positive and nm23-H1-negative groups. Multivariate analysis also showed that nm23-H1 expression was the most significant factor for overall survival of OSCC patients included in this study (P = 0.0007). To further study the role of nm23-H1, a human OSCC cell line (YES-2) was transfected with a plasmid containing a fragment of the nm23-H1 cDNA in an antisense orientation. Reduced expression of nm23-H1 protein in the antisense-transfected (AS) clones was found by Western blot analysis as compared to wild-type YES-2 and YES-2/Neo (clone transfected with the neomycin resistance gene alone). MTT (3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide) assay showed that reduced expression of the nm23-H1 protein in AS clones was consistent with the degree of increased resistance to cisplatin but not etoposide or 5-fluorouracil. These data support the conclusion that reduced expression of nm23-H1 may be associated with resistance to cisplatin, suggesting the value of nm23-H1 expression as a prognostic marker for OSCC patients who are to undergo cisplatin-based chemotherapy.

Bronchoscopic therapy for mucosa-associated lymphoid tissue lymphoma of the trachea.

The tracheal tumor of a 74-year-old female was detected on bronchoscopy and histologically diagnosed as mucosa-associated lymphoid tissue (MALT) lymphoma. We successfully treated the tumor with endoscopic neodyminum-yttruim-aluminium-garnet (Nd-YAG) laser photoresection followed by local ethanol injection. This is the first case in which tracheal MALT lymphoma was successfully treated with bronchoscopy. Bronchoscopic therapy seems to be one of the most valuable strategies for treatment of MALT lymphomas of the central airway.

A novel Na+/Ca2+ channel blocker NS-7 inhibits evoked but not spontaneous dopamine release from rat striatum, as measured by intracerebral microdialysis.

The spontaneous dopamine release from rat striatum, measured by intracerebral microdialysis, was markedly reduced by local perfusion of tetrodotoxin (1 microM) through the dialysis probe. In addition, striatal microinjection of omega-conotoxin GVIA (10 pmol) or omega-agatoxin i.v.A (1 pmol), but not local perfusion of nimodipine, suppressed the spontaneous dopamine release. Therefore, the spontaneous dopamine release may depend on the activity of both Na+ channel as well as N-type and P/Q-type Ca2+ channels. In contrast, local perfusion of a novel Na+- and Ca2+-channel blocker NS-7 (10 microM) did not affect spontaneous dopamine release, whereas it markedly blocked KCl- and veratridine-evoked dopamine release. Therefore, NS-7 may block Na+- and Ca2+-channels only when the ion channels are highly activated.

Synthetic osteochondral replacement of the femoral articular surface.

We have studied damage to the tibial articular surface after replacement of the femoral surface in dogs. We inserted pairs of implants made of alumina, titanium and polyvinyl alcohol (PVA) hydrogel on titanium fibre mesh into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. We discuss the clinical implications of the possible use of this material in articular resurfacing and joint replacement.

Liposomal amikacin: improved treatment of Mycobacterium avium complex infection in the beige mouse model.

Disseminated Mycobacterium avium complex (MAC) infection has reached epidemic proportions and is a major cause of morbidity and mortality in AIDS patients. We have developed a liposomal preparation of amikacin, VS107, which incorporates the drug in 54-65 nm diameter unilameller phospholipid vesicles and is stable at 4 degrees C for more than 4 months. VS107 exhibits superior microbiological and pharmacological activity over the free amikacin and improves the survival of mice in the established model for MAC infection. The serum half-life of VS107 in mice was 9.1 h and a peak serum level of 730 mg/L was obtained after administering three doses of 160 mg/kg. For the therapeutic study, beige mice infected with 10(7) cfu M. avium complex strain 101 were randomised to be treated with placebo liposomes, buffer, free amikacin or VS107 The drugs were administered via the caudal vein thrice weekly for 1, 3, 5 or 7 weeks beginning 5 days after infection. After 51 days of treatment with VS107, the number of viable M. avium in the liver and spleen was a 100 fold lower than was achieved with conventional amikacin (P < 0.01), and more than six decimal logarithms lower than was found untreated controls (P < 0.001). VS107 was well tolerated and might be a suitable candidate for treating human MAC infections.

Genotypes and alkaloid contents of Datura metel varieties.

Datura metel L. var. muricata (BERNH.) DANERT was found to be double recessive with respect to the genes concerning the color and form of the corolla by breeding experiments involving four varieties, i.e. var. metel (white, simple corolla), var. rubra (purple, simple), var. fastuosa (purple, double or triple) and var. muricata (white, purple). The results support the proposal by Danert and others that these variants should be considered as varieties or forms of a single species, Datura metel. The analysis of tropane alkaloids in the seeds, flowers, and leaves of these four varieties showed that scopolamine was always dominant over hyoscyamine. The range of the scopolamine content (% of dry weight) of seeds, flowers, and leaves was 0.294 (var. rubra)-0.631 (var. fastuosa), 0.190 (var. metel)-0.698 (var. rubra), and 0.042 (var. rubra)-0.255 (var.metel), respectively. These findings proved that all the varieties, including var. muricata, which exhibited medium scopolamine content among the varieties, can be utilized as sources of scopolamine.

Bone remodeling around implanted ceramics.

Bone formation and remodeling around implanted materials is influenced by the kind of material, its surface properties, and the anatomical site of implantation. In this study, differences in bone formation around three kinds of ceramics and the importance of the implant location in the tibia were investigated. In the first experiment, we placed three kinds of ceramics--alumina, zirconia and hydroxyapatite (HA)--into the medullary cavity of rabbit tibiae and examined histologically the time-dependent formation of bone around the materials for up to 24 weeks postoperatively. We found that bone formation depends on whether or not the materials are in direct contact with the endosteum. In the second experiment, the same three ceramic materials were implanted transcortically into rabbit tibiae. The bone formed around the implants was most abundant in regions adjacent to the periosteum, followed by the endosteum and the marrow cavity in the approximate ratios of 70%, 40%, and 10%, respectively. In these two experiments, the difference between bioactive and bioinert ceramics could be seen in the interface between the implanted material and the bone. It can be concluded that bone formation around these materials is related to the osteoconductivity of the materials and to the osteogenic capacity of the tissues.

Enzymatic hydrolysis of copoly(N-hydroxypropyl-L-glutamine/L-leucine) hydrogels in vitro.

Two component random copolypeptide hydrogels consisting of N-hydroxyalkyl L-glutamine and L-leucine were prepared by carrying out aminolysis reactions with 3-amino-1-propanol(P) together with cross-linking reactors with 1,8-octamethylenediamine (OMDA) on hydrogels of the starting copolymers consisting of gamma-methyl-L-glutamate(M) and L-leucine(L). The relation between their bulk structure and properties was investigated with regard to the swelling ration in water, aqueous vapor permeability, tensile properties, and enzymatic degradation behavior in a pseudoextracellular fluid (PECF). The tensile property of the hydrogels was highly dependent on the swelling ratio in PECF, and on the hydrophobicity of the side chains, whose behavior was typical of an elastomer. It was shown that a common relation was obtained between the rate of water vapor permeabilities and the swelling ratio of hydrogels in PECF regardless of the difference of the nature of side chains. Biodegradation of the hydrogels in vitro by bromelain indicated that the degradation took place in bulk rather than on surface, and that the rate of degradation was also highly dependent on the swelling ratio of samples as well as on the hydrophobicity of the side chains of samples.

Irinotecan (CPT-11) and characteristic mucosal changes in the mouse ileum and cecum.

BACKGROUND: Irinotecan--or CPT-11; 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptotheci n--is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is severe diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established. Cisplatin (CDDP; cis-diamminedichloroplatinum) and CPT-11 exhibit synergistic antitumor activity and have been used in combination-chemotherapy regimens. Single-agent chemotherapy with conventional doses of CDDP does not cause clinically relevant diarrhea. PURPOSE: To elucidate the mechanisms of induction of diarrhea by high-dose CPT-11 and to compare them with those of diarrhea induced by high-dose CDDP, we used histopathologic and immunohistochemical methods to examine the intestines of mice treated with either CPT-11, CDDP, or saline (control). METHODS: Male ICR mice were administered intraperitoneally either 100 mg/kg CPT-11 daily for 4 days, 10 mg/kg CDDP daily for 3 days, or phosphate-buffered saline (control) daily for 4 days (10 mice per group). Preliminary experiments indicated that diarrhea was induced in mice approximately 6 days after administration of CPT-11 or CDDP; therefore, in the experiments described, animals were killed 6 days after the first dose. Serial paraffin-embedded sections of the intestine were stained with hematoxylin-eosin, Grimelius (to identify endocrine cells), or high-iron diamine-alcian blue (stains sialomucin blue and sulfomucin brown-black). Immunohistochemical analyses were performed with the use of anti-proliferating cell nuclear antigen (anti-PCNA; to assay proliferation), anti-Le(y) (BM-1; indirect measure of apoptosis), and anti-synaptophysin antibodies (to identify the enteric nervous system and enterochromaffin cells). A terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) method was used to detect DNA fragmentation in situ (i.e., apoptosis). The concentrations of two intestinally active secretogogues, plasma serotonin and vasoactive intestinal polypeptide, were also measured. RESULTS: The levels of plasma intestinal hormones were similar in control, CPT-11, and CDDP groups. No active necrotic changes were observed in the intestines of CPT-11- and CDDP-treated mice, even though marked thinning of the intestinal walls was observed in both cases. The intestines of CPT-11-treated mice, but not those of control or CDDP-treated mice, were characterized by epithelial vacuolation of the ileum (associated with increased apoptosis as measured by BM-1 and TUNEL) and goblet-cell hyperplasia with excessive amount of sulfomucin in the cecum (suggesting induction of differentiation). By contrast, CDDP treatment of mice reduced the number of villi in the jejunum and destroyed crypt cells containing large Paneth (secretory) granules in the ileum. CONCLUSIONS: CPT-11 may produce characteristic mucosal changes in the intestine by inducing apoptosis and cell differentiation. The observed changes are likely to cause malabsorption of water and electrolytes and hypersecretion of mucin. These structural and functional effects are probably the main causes of CPT-11-induced diarrhea. CDDP appears to cause diarrhea in mice by causing diffuse mucosal damage in the intestines.

Transmission electron microscopy observations at the interface of bone and four types of calcium phosphate ceramics with different calcium/phosphorus molar ratios.

Four kinds of calcium phosphate ceramics, beta-calcium pyrophosphate (Ca2P2O7), beta-tricalcium phosphate (Ca3(PO4)2), hydroxyapatite (Ca10(PO4)6(OH)2) and tetracalcium phosphate (Ca4(PO4)2O), were prepared. The calcium/phosphorus molar ratios were 1, 1.5, 1.66 and 2, respectively. Particles (150-300 microns) of these ceramics were packed into holes (diameter 2.5 mm) made in the tibial metaphysis of mature male rats. At 2 weeks, 4 weeks, 8 weeks and 6 months after the operation, undecalcified specimens were prepared. Transmission electron microscopy showed that the bone-bonding behaviour of calcium phosphate ceramics at the interface with bone did not vary with the calcium/phosphate molar ratio. Amorphous substances or needle-like microcrystals were observed on the surface of the ceramics at 2 weeks after implantation. The ceramics showed direct continuity with small crystallites of bone tissue at 4 weeks, 8 weeks and 6 months after implantation. The ceramics appeared to be getting smaller with time. Collagen fibres were not observed at the bone/ceramic interface. Neither chemical bonding nor mechanical bonding by interlocking between bone and ceramics was described by morphological observation using transmission electron microscopy.

Combined treatment of autoimmune MRL/MP-lpr/lpr mice with a herbal medicine, Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to) plus suboptimal dosage of prednisolone.

Therapeutic effects of combined treatment with a Chinese medicine prescription, Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NYT) and suboptimal doses of prednisolone (PSL) on pathological findings of autoimmune-prone MRL/lpr mice were examined. Six-week-old MRL/lpr mice were treated orally with 1000 mg/kg of NYT, 0.5 or 2 mg/kg of PSL, 1000 mg/kg of NYT plus 0.5 or 2 mg/kg of PSL (combined treatment) or solvent only (control) six times per week. The rates of signs and symptoms of autoimmune disease (lymphadenopathy, proteinuria, dermatitis, loss of hair) were suppressed significantly in groups given PSL (2 mg/kg) alone, NYT alone and combined treatment with PSL (2 mg/kg) plus NYT (1000 mg/kg) compared with control, respectively, whereas treatment with PSL (0.5 mg/kg) alone did not inhibit their occurrence. ConA response and IL-2 production were also improved significantly in lymphocytes of mice given the combined treatment. Interestingly, treatment with NYT alone enhanced further the augmented IFN-gamma production in MRL/lpr mice but the combined treatment suppressed such an augmented production. The combined treatment dramatically reduced the level of anti-DNA antibodies in serum of MRL/lpr mice. By contrast, NYT alone treatment had no effect on autoantibodies production. These results suggest that combined treatment with NYT plus a suboptimal dose of PSL could be effective for systemic lupus erythematosus without severe side-effects.

Hyperthermic treatment of canine tibia through RF inductive heating of an intramedullary nail: a new experimental approach to hyperthermia for metastatic bone tumours.

Although the incidence of metastatic bone tumours is recently increasing, the local control rate of conventional treatment modalities is not satisfactory. If an intramedullary nail for the fixation of a weakened bone with metastatic lesions can be used as a heat-generating material for hyperthermia, the treatment result is expected to improve. This new approach to hyperthermic treatment of bone tumours has been investigated in a canine tibia. An intramedullary nail made of stainless steel was put into a medullary canal of a canine tibia. The leg was exposed to an alternating magnetic field of 100 kHz in the frequency and 100 Oe in the maximum intensity. The nail was inductively heated for 60 min. The temperature of the nail > 50 degrees C and the cancellous bone 5 mm from the nail was heated to a therapeutic temperature, 42.5 degrees C. After a bone labelling with tetracycline and calcein, the dogs were killed 2, 4 and 12 weeks after the heating. The area of osteonecrosis was evaluated by fluorescence microscopy analysis. The heated cancellous bone around the nail showed osteonecrosis in 2 weeks after the treatment, but it recovered completely in 12 weeks. This experiment has demonstrated the heating capability of the new hyperthermic technique and minimal toxicity to the bone, and suggests the clinical application to metastatic bone tumours.