In vivo bactericidal activities of Japanese rice-fluid against H. pylori in a Mongolian gerbil model.

PURPOSE: The antibiotic effect of rice-fluid on Helicobacter pylori infection was investigated using a Mongolian gerbil model. METHODS: Gerbils were divided into four groups: H. pylori -infected, rice-fluid-treated animals (group A); H. pylori -infected, untreated animals (group B); uninfected, rice-fluid-treated animals (group C); and uninfected, untreated animals (group D). Group A and B animals were killed 14 weeks after H. pylori infection and group C and D animals were killed at the same age. The stomachs were examined for histology, 5'-bromo-2'-deoxyuridine (BrdU) labeling, and the bacterial burden. Serum anti-H. pylori antibody titers were also tested. RESULTS: The positive incidence of H. pylori -culture was 25 and 84 % in groups A and B, respectively (p<0.01). Both the degree of inflammation and the BrdU labeling index in group A were significantly lower than those in group B. CONCLUSIONS: Rice-fluid showed an antibiotic effect on H. pylori and an anti-inflammatory effect on the H. pylori -associated gastritis.

In vitro bactericidal activities of Japanese rice-fluid against Helicobacter pylori strains.

BACKGROUND: Helicobacter pylori has now been widely recognized as a causative agent of gastroduodenal diseases. The development of safer anti- H. pylori compounds is desirable due to the antibiotic-resistant strains emerged to date. METHODS: We successfully developed the compounds of Rice-fluid derived from unpolished, polished, and usually cooked Japanese rice, and investigated their in vitro antibacterial activities by means of the Time-Kill-Curve methods against various species of bacteria including H. pylori strains. RESULTS: All of the compounds revealed keen bactericidal activities against H. pylori, followed by Streptococcus pneumoniae and Campylobacter jejuni strains, but failed to affect the viability of other bacterial species investigated including staphylococci, enterococci, Pseudomonas aeruginosa, and other gram-negative rods belonging to the family Enterobacteraceae. The bactericidal activities were demonstrated to be time- and concentration-dependent. CONCLUSIONS: The compounds of Rice-fluid are considered to be potentially new and safe therapeutic regimens against H. pylori infections. The mechanism of their bactericidal activities against H. pylori strains remains to be elucidated.

Involvement of two genetic lineages of Sarcoptes scabiei mites in a local mange epizootic of wild mammals in Japan.

Similar to wild mammals on the continents, mange caused by the mange mite, Sarcoptes scabiei (Acari: Sarcoptidae) is spreading in wild mammals in most of Japan. We collected crusted or alopetic skin from 120 raccoon dogs (Nyctereutes procyonoides viverrinus), three raccoons (Procyon lotor), six Japanese badgers (Meles anakuma), one Japanese marten (Martes melampus), one stray dog (Canis lupus familiaris), four wild boars (Sus scrofa leucomystax), and one Japanese serow (Capricornis crispus), mainly in an area where mangy wild animals have been increasingly noted in the past 4 yr. The second internal transcribed spacer (ITS2) region of the ribosomal RNA gene and the partial 16S and cytochrome c oxidase subunit I (cox-1) genes of mitochondrial DNA (mtDNA) were characterized in these skin samples. The ITS2 sequencing (404 base pairs [bp]) identified the causative mite for mangy skin lesions of 128 animals as S. scabiei, regardless of host origin. The cat mite (Notoedres cati) was the cause in one raccoon dog and one raccoon. Most mites had almost identical ITS2 nucleotide sequences to those recorded in a variety of mammals worldwide. Partial 16S and cox-1 fragments of mtDNA amplified and sequenced successfully (331 bp and 410 bp, respectively) showed an identical nucleotide sequence except for one site (C vs. T) for the former and four sites (G, C, C, C vs. A, T, T, T, respectively) for the latter fragment. These substitutions were always synchronized, with the two mitochondrial DNA haplotypes (i.e., C/GCCC and T/ATTT) appearing to separately colonize in geographic units. The T/ATTT haplotype fell into a clade where animal-derived mites worldwide dominated, whereas the C/GCCC haplotype formed a geographic branch unique to Japanese isolates. These results suggest that heterologous populations of monospecific S. scabiei are expanding their populations and distributions regardless of host species in an apparently local mange epizootic of wild mammals in Japan.

The design of polymer microcarrier surfaces for enhanced cell growth.

A variety of neutral and cationic polymers based on polyamino acids were prepared and investigated as microcarriers for cell attachment and growth. Among neutral polymer particles including the alkylated poly(gamma-methyl L-glutamate) (PG) particles, in which the hydrophobicity changes as a function of the length of the alkyl groups, and hydroxy terminal PG particles, the PG particle with the longest alkyl chain (PG-C12) demonstrated the highest cell attachment rate and highest rate of cell growth. Moreover, the introduction of hydroxyl groups (PG-OH) led to a deterioration of cell growth. Cell growth on cationic particles having primary amino groups was drastically dependent upon the anion exchange capacity (AEC). A higher AEC for aminated PG microcarriers inhibited cell growth. In contrast, a higher AEC for cross-linked poly( epsilon -lysine) (PL) microcarriers facilitated cell growth. Cell growth on cationic particles clearly showed a good correlation with the pK(a,app) of the microcarriers, but not with their AEC. The particles with low and high pK(a) values possessed toxically acidic and basic pH microenvironments near the surface, respectively. These microenvironments had cytotoxic effects. On the other hand, no correlation between attachment rate constants and high cell growth was observed. The aminated particles, in which pK(a) were controlled at neutral pH, and PG-C12 produced obviously higher cell growth than did a commercially available microcarrier.

Randomized phase II study of primary systemic chemotherapy and trastuzumab for operable HER2 positive breast cancer.

BACKGROUND: In primary systemic therapy in patients with human epidermal growth factor receptor 2 positive (HER2(+)) breast cancer, improvements in pathologic complete response (pCR) rate have been achieved by administering trastuzumab. PATIENTS AND METHODS: Patients with stage II or IIIA HER2(+) operable breast cancer were randomly assigned to receive four 3-weekly cycles of FEC (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)) followed by 4 cycles of 3-weekly trastuzumab (8 mg/kg week 1 and then 6 mg/kg) with either 12 weekly doses of paclitaxel 80 mg/m(2) (FEC-PH) or 4 cycles of 3-weekly docetaxel 75 mg/m(2) (FEC-DH). RESULTS: Between March 2007 and June 2008, 102 patients were enrolled. Forty-nine patients receiving FEC-PH and 47 receiving FEC-DH were assessable for efficacy and safety. Eighty-four patients completed treatment and underwent surgery. There was no significant difference in the pCR rate between the 2 groups (46.9% [95% CI, 33.7%-60.6%] with FEC-PH vs. 42.6% [95% CI, 29.5%-56.8%] with FEC-DH; P = .67). Analysis by hormone receptor (HR) status showed pCR rates of 54.2% (32/59) in HR(-) tumors and 29.7% (11/37) in HR(+) tumors (P = .02). Among HR(-) tumors, the pCR rates were 65.4% and 45.5% in patients treated with FEC-PH and FEC-DH, respectively (P = .13). CONCLUSIONS: There was no significant difference in pCR rate between FEC-PH and FEC-DH. Both regimens achieved higher pCR rates in HR(-) than HR(+) breast cancer, and there was a trend toward higher pCR in HR(-) tumors with FEC-PH compared with FEC-DH. Further investigation is warranted to explore the relationship between efficacy and HR status.

Chiral scandium catalysts for enantioselective Michael reactions of beta-ketoesters.

A highly enantioselective Michael reaction of beta-ketoesters with alpha,beta-unsaturated ketones promoted by a chiral scandium catalyst has been developed. In the presence of Sc(OTf)3 and (S,S)-6,6'-bis(1-hydroxy-2,2'-dimethylpropyl)-2,2'-bipyridine, the desired Michael reactions proceeded smoothly in dichloroethane at 40 degrees C to afford the corresponding adducts in good to high yields with excellent enantioselectivities in most cases. It was found in this reaction that a lower concentration of the reaction mixture was key to attaining high enantioselectivities.