Colistin Resistance of Pseudomonas aeruginosa Isolated from Snakes in Taiwan.

This study included fifty-eight isolates of P. aeruginosa from the oral cavity of snakes that were recruited from clinical cases, captive and wild snakes. The minimum inhibitory concentrations (MICs) for the determination of susceptibility were identified by the broth microdilution method. Polymerase chain reaction (PCR) was employed to detect ß-lactamases genes. With regard to antipseudomonal antibiotics, the lowest nonsusceptible rates were in aztreonam (15%), piperacillin/tazobactam (12%), and amikacin (9%). The nonsusceptible rates were high in gentamicin (33%) and colistin (55%). Meanwhile, blaTEM presented in 100% of isolates where blaAmpC, blaOXA-1, and blaOXA-10 came at 94.8%, 89.7%, and 27.6%, respectively. Emergence of multidrug resistant (MDR) strains and colistin-resistant strains highlights the potential breach of public health as P. aeruginosa could be transmitted through either direct contact or indirect dissemination through the environment. This study reports that the highly resistant P. aeruginosa from snakes' oral cavity were discovered for the very first time in Taiwan.

Asparagus polysaccharide and gum with hepatic artery embolization induces tumor growth and inhibits angiogenesis in an orthotopic hepatocellular carcinoma model.

Liver cancer is one of leading digestive malignancies with high morbidity and mortality. There is an urgent need for the development of novel therapies for this deadly disease. It has been proven that asparagus polysaccharide, one of the most active derivates from the traditional medicine asparagus, possesses notable antitumor properties. However, little is known about the efficacy of asparagus polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported that asparagus polysaccharide and its embolic agent form, asparagus gum, significantly inhibited liver tumor growth with transcatheter arterial chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC) tumor model, while significantly inhibiting angiogenesis and promoting tumor cell apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions and showed little toxicity to the host. These results highlight the chemotherapeutic potential of asparagus polysaccharide and warrant a future focus on development as novel chemotherapeutic agent for liver cancer TACE therapy.

Synthesis and antibacterial activity of new fluoroquinolones containing a cis- or trans-cyclohexane moiety.

New quinolone derivatives bearing a cis- or trans-cyclohexane side chain at the C-7 position have been synthesized and evaluated for their antibacterial activities against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa using the agar dilution method. The activities of compound 53 against these three bacteria were superior to those of the reference drug lomefloxacin. Compounds bearing a cis-cyclohexane side chain generally exhibited greater antibacterial activity than their corresponding trans-isomers.

Ethyl 7-amino-1-cyclo-propyl-6-fluoro-8-meth-oxy-4-oxo-1,4-dihydro-quinoline-3-carboxyl-ate monohydrate.

In the title compound, C(16)H(17)FN(2)O(4)·H(2)O, the dihedral angle between the heterocyclic ring and the benzene ring is 5.77 (9)°, that between the heterocycle and the ethoxy-carbonyl plane is 15.5 (1)°, and that between the heterocyclic ring and the cyclopropane ring is 67.75 (13)°. In the crystal structure, mol-ecules are linked into a ribbon-like structure along the c axis by N-H⋯O and O-H⋯O hydrogen bonds.

[Synthesis of 5-fluorouracil derivatives containing alkanoic acid].

OBJECTIVE: To synthesize 5-fluorouracil derivatives containing 2-5 carbon alkanoic acid. METHODS: N1-substituted derivatives containing alkanoic acid were prepared through the hydrolysis of these products of the reaction of haloesters and excessive amount of 5-fluorouracil. 5-fluorouracil were protected with tertbutoxycarbonyl (Boc) at N1-position, then reacted with haloesters and deprotected in turn, through this "one-pot" method, N3-substituted 5-FU alkanoic acid esters can be obtained, with high yields (75%-85%). The hydrolysis of these products gave N3-substituted 5-FU alkanoic acid at last. RESULTS: Including 10 new compounds and 8 aim compounds, 16 derivatives of 5-fluorouracil were obtained and confirmed by the spectral detection. CONCLUSIONS: The reaction of excessive amount of 5-fluorouracil and haloesters can produce a good yield of N1-substituted derivatives. N3-substituted derivatives can be obtained through the reactions of 5-fluorouracil protected with Boc at N1-position and haloesters.

[Study on the determination of piperazinylethylestrone].

OBJECTIVE: To establish an HPLC method and a non-aqueous titration for the determination of piperazinylethylestrone drug substance, and an HPLC method for the determination of piperazinylethylestrone in dog plasma. METHODS: Anhydrous acetic acid as solvent, 0.1 mol/L perchloric acid as titrant, crystal violet solution as indicator to establish non-aqueous titrations and ODS column as stationary phase, methanol and a mixture of 0. 025 mol/L sodium phosphate monobasic and 0.02 mol/L sodium dedecyl sulfate (80:20) [adjusted with phosphoric acid to a pH (4.8 +/- 0.1)] as mobile phase, 220 nm as detective wavelength to establish HPLC-UV method for determination of piperazinylethylestrone drug substance; FMOC-CL as a derivatization reagent, FD as a detector to establish an HPLC method with derivatization and column switching for determination of piperazinylethylestrone in dog plasma. RESULTS: The RSD of non-aqueous titrations within-day and between-day were 0.28% and 0.21%, respectively; the established HPLC-UV method had good linearity and precision within the range of 1.001-5.005 microg of piperazinylethylestrone, the detection limit was 4 ng (S/N=3); the linearity of HPLC method with derivatization and column switching was within the range of 8.4-420 ng/ml, the detection limit was 1 ng (S/N=3). The clean-up recoveries were from 77.24% to 83.10%, and the method recoveries were 98.33%-103.3%. The RSD of within-day and between-day were less than 7.7% and 7.3%, respectively. CONCLUSION: The above three methods are simple, accurate and precise for the determination of piperazinylethylestrone drug substance and for the determination of piperazinylethylestrone in dog plasma.

[Bone histomorphometry study on lumbar vertebrae microstructure of ovariectomized goats].

OBJECTIVE: To demonstrate the histomorphometric changes of postmenopausal osteoporosis (PMO) goat model after bilateral ovariectomy (OVX). METHODS: Fifteen female goats were randomly enrolled into four groups: 3 goats without any treatment (group C), 3 goats sham-operated only (group S), 4 goats 6 months after OVX (group OVX6M), 5 goats 18 months after OVX (group OVX18M). On the 21st and 9th day prior to sacrifice, tetracycline was given to them in order to label the bone for dynamic study. The first lumbar vertebrae from each goat were reserved for bone histomorphometric study. RESULTS: As compared with group C and S, the trabecular bone volume (TBV)/total tissue volume, TBV/sponge bone volume, mean trabecular plate thickness (MTPT) and mean trabecular plate density in OVX6M and OVX18M groups were significantly lower (P < 0.01, but MTPT: P < 0.05), while the mean trabecular plate space, surface/volume ratio of the trabecular bone, single labelled surfaces [Sfaces(s)], double labelled surfaces [Sfaces(d)], Sfaces (d + 1/2s), mean osteoid seam width, mineralization lag time, speed of bone formation in the tissue levela and osteoid maturation period were significantly higher (P < 0.01). CONCLUSION: In OVX goats, bone loss accelerated, resulting in destroyed bone microstructure, fasten frequency of activation and high bone turnover. Therefore, the bone resorption process exceeds over the bone formation, successfully establishing a high turnover osteoporotic metabolic model.

[Piperazinyl estrone prevents bone loss in ovariectomized rats].

AIM: To determine the effect of piperazinyl estrone, a new estrogen derivative, on bone turnover, bone mass and uteri in ovariectomized rats. METHODS: Female Sprague-Dawley rats were ovariectomized (OVX) or sham operated (sham) at the age of 3 months and treated with estrone (E) at 0.75 mg.kg-1.d-1, or with piperazinyl estrone (P-E) at 1 or 10 mg.kg-1.d-1, orally, for 3 months. At the time of death, the uterine weight was measured. Bone histomorphometric analysis of proximal tibial metaphyses (PTM) was performed in undecalcified sections. RESULTS: Bone histomorphometric data showed that the percent trabecular area (% Tb.Ar) of OVX rats with bone high turnover was significantly decreased. The uteri were atrophied. The percent trabecular area (% Tb.Ar) of estrone treated group was increased in decreasing bone turnover manner. But the size and weight of uteri in this group were increased vs OVX group. The bone loss induced by OVX was preserved by P-E treatment, but the mechanism of maintaining bone is different from that of E-treated rats. P-E treatment in low dose did not decrease any bone formation indices, such as percent labeling perimeter, bone formation rate per bone volume (BFR/BV), except bone mineral apposition rate (MAR) compared with E-treated group, and maintained them at OVX level. The uteri were found to be in atrophy compared with the match dose (0.75 mg) of E-treated OVX rats. But rats treated with high dose of P-E showed the same change like E-treated group. CONCLUSION: The finding of this study shows that lower dosage of piperazinyl estrone has effect on preventing the bone losses in OVX rats, while the bone formation and the uterus are not affected, thus supporting the hypothesis that piperazinyl estrone has the potential to prevent postmenopausal bone loss in women with less side effects.

Effects of low doses of hydrochloride tetracycline on bone metabolism and uterus in ovariectomized rats.

AIM: To study the effects of low doses of hydrochloride tetracycline (Tc) on bone metabolism and uterus in the ovariectomized (Ova) rats. METHODS: Forty 3-month-old rats were randomly divided into 5 groups: sham group, Ova group, Tc1 group (1.2 mg/kg/d), Tc2 group (4.8 mg/kg/d), and estrone group (1.48 mg/kg/d), oral fed for 3 months. The proximal tibia metaphyses were processed undecalcified for quantitative bone histomorphometry and the soft tissues were processed in paraffin for pathological observation. RESULTS: Placebo-treated (lactose) Ova rats were characterized by trabecular area (TA) decreasing and their architecture worsening compared with sham controls, and bone resorption was over formation with high bone turnover. The uteri were atrophy. (2) In estrone-treated group, TA and trabecular numbers were significantly increased and the trabecular separation decreased vs Ova group. Estrone slowed down Ova-inducing bone high turnover. But the size, weight, and the endometrium of the uteri in this group were increased vs Ova group. (3) TA was increased in both Tc1 and Tc2 groups compared with Ova rats. Tc maintained bone formation indices almost at Ova level, and only decreased mineral apposition rate (MAR) in Tc1 group, and declined bone resorption perimeter. The uteri and the cell of liver and kidney almost maintained at Ova level; Tc2 decreased labeling perimeter and increased MAR in comparison with Tc1 group. The uteri were atrophy, whose size maintained at Ova level; yellow labeling was not found in bone with these doses of Tc, while yellow labeling could be seen with the doses of 30 mg/kg/d of Tc for bone marker. CONCLUSION: The two doses of Tc have similar effects on preventing bone loss in Ova rats while the bone formation and uterus are not affected. However, Tc2 does not have more effects on increasing bone mass, Tc2 causes less mild damages to the liver and kidneys.

C-mycprotein expression upregulated by 2-(3-estrone-N-ethyl piperazine-methyl) tetracycline in bone.

AIM: To study the effect of XW630 on expression of pro-oncogene c-myc in the long bones of fetal mice in vitro for postulating the mechanism by which XW630 exerts its effect on bone. METHODS: The fetuses of pregnant mice were removed on day 16 of gestation, the long bones of the forelimbs of female fetal mice were freed of muscle and soft tissue and cultured in a specific device for 48 h in BGJb medium treated with 1 x 10(-7), 1 x 10(-8) and 1 x 10(-9) mol.L-1 XW630 in the final medium. After cultured for 48 h, the long bones were harvested and immunohistochemical analysis was performed for determination of c-Myc protein expression in epiphyseal plates. The areas of positive cells in the resting zone, proliferative zone and hypertrophic zone in epiphyseal plate were determined under image analytic system. RESULTS: When the concentration of XW630 in the medium was 1 x 10(-9) mol.L-1, the area of c-Myc positive cells increased in the proliferative zone compared with 1 x 10(-9) mol.L-1 in the estrone group, significant increase was also observed in the resting zone compared with the control group. When the concentration of XW630 in medium was 1 x 10(-8) or 1 x 10(-7) mol.L-1, stronger expression than that in the control group and the estrone group at the same concentration was observed in each of the three zones. CONCLUSION: The estrogenic effect of XW630 on bone was stronger than that of estrone. XW630 may promote proliferation and differentiation of chondroncytes by promoting c-Myc protein expression in chondroncytes. Thus, endochondral bone formation was enhanced.