Budesonide enema in pouchitis--a double-blind, double-dummy, controlled trial

BACKGROUND: Pouchitis has been suggested to be a recurrence of ulcerative colitis in a colon-like mucosa. Topical steroids are a valid therapeutic alternative for distal forms of ulcerative colitis. AIM: To investigate the efficacy and tolerability of budesonide enema in the treatment of pouchitis compared with oral metronidazole. MATERIALS AND METHODS: Twenty-six patients with an active episode of pouchitis (defined as a pouchitis disease activity index score >or= 7) and no treatment during the previous month were randomized to receive either budesonide enema (2 mg/100 mL at bedtime) plus placebo tablets or oral metronidazole (0.5 g b.d.) plus placebo enema in a prospective, double-blind, double-dummy, 6-week, controlled trial. RESULTS: Based on the intention-to-treat principle, we detected a significant improvement in disease activity at the end of the first week with both drugs (P < 0.01). After that, improvement was moderated until stabilization at 4 weeks in both treatments. The per protocol analysis showed that both drugs had similar efficacy in terms of disease activity, clinical and endoscopic findings. Fifty-eight per cent and 50% of patients improved (decrease in pouchitis disease activity index >or= 3) with budesonide enema and metronidazole, respectively (odds ratio, 1.4; confidence interval, 0.2-8.9). Adverse effects were observed in 57% of patients given metronidazole and in 25% of patients given budesonide. CONCLUSIONS: Budesonide enemas are an alternative treatment for active pouchitis, with similar efficacy but better tolerability than oral metronidazole.     

Flow cytometric estimation on cytotoxic activity of leaf extracts from seashore plants in subtropical Japan: isolation,quantification and cytotoxic action of (-)-deoxypodophyllotoxin

The cytotoxic activity of methanol extracts of leaves collected from 39 seashore plants in Iriomote Island, subtropical Japan was examined on human leukaemia cells (K562 cells) using a flow cytometer with two fluorescent probes, ethidium bromide and annexin V-FITC. Five extracts (10 microg/mL) from Hernandia nymphaeaefolia, Cerbera manghas, Pongamia pinnata, Morus australis var. glabra and Thespesia populnea greatly inhibited the growth of K562 cells. When the concentration was decreased to 1 microg/mL, only one extract from H. nymphaeaefolia still inhibited the cell growth. A cytotoxic compound was isolated from the leaves by bioassay-guided fractionation and was identified as (-)-deoxypodophyllotoxin (DPT). The fresh leaves of H. nymphaeaefolia contained a remarkably high amount of DPT (0.21 +/- 0.07% of fresh leaf weight), being clarified by a quantitative HPLC analysis. DPT at 70-80 pM started to inhibit the growth of K562 cells in an all-or-none fashion and at 100 pM or more it produced complete inhibition in all cases. Therefore, the slope of the dose-response curve was very steep. DPT at 100 pM or more decreased the cell viability to 50%-60% and increased the number of cells undergoing apoptosis (annexin V-positive cells). The results indicate that DPT contributes to the cytotoxic action of the extract from the leaves of H. nymphaeaefolia on K562 cells.     

Etiology and susceptibility of urinary tract isolates in Kosova

Urinary tract infections are amongst the most common pathogenic infections with an increasing resistance to antimicrobials. The objective of this study was to determine the etiology and antimicrobial susceptibility patterns of urinary tract infection pathogens isolated in Kosovo. A retrospective study was carried from urine samples of both inpatients and outpatients that were received in our laboratory throughout 2001. During the study period, 16500 urine samples were analysed, of which 4260 (25.8%) had significant bacteriuria obtained from 1420 patients. Of this, 1059 (74.6%) were collected from females and 361 (25.4%) from males. Urine samples processed from outpatients were 72.5% (1029), whereas 27.5% (391) were from hospitalised patients. Escherichia coli was the most common aetiologic agent isolated (80.5%), followed by Proteus spp. (6.1%), Klebsiella spp. (5.9%), Citrobacter (5.1%) and Mycobacterium tuberculosis (0.8%). Gram-positive bacteria accounted for only 0.3%. Pseudomonas aeruginosa was only isolated from inpatients and was responsible for 0.6% of infections. Amoxicillin, ampicillin and trimethoprim-sulphamethoxazole resistance rates were 48.7, 46.5 and 32.1%, respectively. Nitrofurantoin, cefalexin and ciprofloxacin expressed the highest susceptibility among these isolates. E. coli isolates from inpatients and outpatients showed more than 25% resistance to trimethoprim-sulphamethoxazole. Of all isolates, 16% (225) were resistant to three or more agents and considered multi-drug resistant. Current data on the prevalence of multidrug resistance among urinary tract isolates should be a consideration to change the current empiric treatment of urinary tract infections.     

γ-Hydroxybutyric acid and 5-fluorouracil, metabolites of UFT, inhibit the angiogenesis induced by vascular endothelial growth factor

UFT, a drug composed of uracil and tegafur at the molar ratio of 4:1, is an orally active agent for the treatment of a wide variety of malignant tumours. Using a murine dorsal air sac (DAS) assay, we have previously shown that UFT and its metabolites, γ-hydroxybutyric acid (GHB) and 5-fluorouracil (5-FU), inhibited the angiogenesis induced by murine renal cell carcinoma. Here we report that UFT was more effective than other fluorinated pyrimidines such as 5-FU and doxifluridine (5^′-DFUR) in blocking the angiogenic responses elicited by five human cancer cell lines which produced high levels of vascular endothelial growth factor (VEGF), but no detectable fibroblast growth factor-2 (FGF-2) in vitro. In contrast, UFT was unable to block the angiogenic response to one human gastric cancer cell line which produced both VEGF and FGF-2 in vitro. However, the production or secretion of VEGF by these cells was unaffected by GHB and 5-FU treatment. Interestingly, GHB suppressed the chemotactic migration and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated by VEGF, without inhibiting their DNA synthesis. Since GHB did not affect the FGF-2-driven activities in HUVECs, its action appears to be VEGF-selective. On the other hand, 5-FU inhibited DNA synthesis and migration of HUVECs stimulated by both VEGF and FGF-2, and tube formation driven by VEGF, suggesting that 5-FU is cytotoxic to endothelial cells. The inhibitory effects of 5-FU, and especially those GHB, were reproduced under in vivo condition using the DAS assay. The VEGF-mediated angiogenesis was significantly inhibited by UFT, 5-FU, and especially by GHB. We propose that the selective inhibitory effects of GHB on VEGF-mediated responses of endothelial cells are involved in the anti-angiogenic activity of UFT. This revised version was published online in June 2006 with corrections to the Cover Date.     

Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide

Effect of Ginkgo biloba extract was examined on dissociated rat cerebellar neurons suffering from oxidative stress induced by hydrogen peroxide using a flow cytometer and ethidium bromide. Hydrogen peroxide at a concentration of 3 mM increased the number of neurons stained with ethidium (presumably dead neurons) in a time-dependent manner. Pretreatment of neurons with G. biloba extract (10 μg/ml greatly delayed a time-dependent increase in number of dead neurons during exposure to hydrogen peroxide. It was true, but less effective, in the case of treatment with G. biloba extract immediately or 60 min after start of oxidative stress. Results implicate G. biloba extract as a potential agent in protecting the neurons suffering from oxidative stress induced by hydrogen peroxide.     

Intraocular pressure change during hemodialysis

PURPOSE: To evaluate intraocular pressure (IOP) change through hemodialysis and examine other factors to affect IOP change in patients treated with hemodialysis. DESIGN: Prospective, observational case series. METHODS: IOP, blood pressure, and plasma colloid osmotic pressure (COP) were measured in 188 eyes of 95 patients receiving hemodialysis in Nantan General Hospital. RESULTS: IOP significantly decreased after hemodialysis (P = 0.006). Body weight, systolic and diastolic blood pressure also decreased significantly (P < 0.001). COP significantly increased (P < 0.001). Change in IOP correlated negatively with COP change (OD; r = -0.196, OS; r = -0.339) and positively with change in body weight (OD; r = -0.278, OS; r = -0.357). IOP tended to increase after hemodialysis in patients receiving hemodialysis for more than 12 years. CONCLUSIONS: IOP decrease during hemodialysis may be due to COP increase. Patients receiving hemodialysis for a long time are more likely to show IOP increase after hemodialysis.     

流式细胞术检测初治急性白血病患者VEGFR1和R2的表达及其意义

目的:了解初治急性白血病(AL)患者骨髓不同类型细胞表达VEGFR1和VEGFR2的情况,探讨流式细胞术检测白血病细胞VEGFR表达的意义。方法:采用流式细胞术CD45/SSC设门方法检测27例初治AL患者骨髓淋巴细胞、粒细胞、白血病细胞和10例正常对照者骨髓淋巴细胞、粒细胞VEGFR1、VEGFR2、VEGFR1/VEGFR2的表达。结果:VEGFR1在初治AL组与正常对照组淋巴细胞之间或粒细胞之间表达差异无统计学意义(P>0.05);在初治AL组,VEGFR1在淋巴细胞的表达高于在粒细胞或在白血病细胞的表达(P<0.05),但在粒细胞与白血病细胞之间表达差异无统计学意义(P>0.05);在正常对照组,VEGFR1在淋巴细胞的表达高于在粒细胞的表达(P<0.05)。VEGFR2、VEGFR1/VEGFR2在初治AL组和正常对照组淋巴细胞之间、粒细胞之间、淋巴细胞与粒细胞之间、淋巴细胞与白血病细胞之间以及粒细胞与白血病细胞之间表达均差异无统计学意义(均P>0.05)。VEGFR1、VEGFR2、VEGFR1/VEGFR2在初治急性淋巴细胞白血病(ALL)组与初治急性髓细胞白血病(AML)组白血病细胞之间表达差...     

氟伐他汀对高糖诱导人足细胞血管内皮生长因子表达的影响及机制

目的探讨氟伐他汀对高糖诱导的人足细胞血管内皮生长因子(VEGF)表达的影响及机制。方法体外培养人足细胞,随机分为A组(正常糖组)、B组(高糖组)、C组(高糖+氟伐他汀10-7mol/L组)、D组(高糖+氟伐他汀10-6mol/L组)、E组(高糖+氟伐他汀10-5mol/L组)和F组[高糖+胞外信号调节激酶(ERK)抑制剂PD98059组]。用Western blot检测VEGF和磷酸化ERK1/2(pERK1/2)蛋白表达。结果 B组VEGF、pERK1/2表达较A组明显升高,并呈时间依赖性(P<0.05)。F组VEGF、pERK1/2表达较B组显著降低(P<0.01)。与B组比较,C、D、E组VEGF及pERK1/2表达亦明显减少,并呈浓度依赖性(P<0.05)。结论高糖刺激体外培养人足细胞VEGF表达增加,氟伐他汀可减少高糖诱导的VEGF表达,其机制可能与氟伐他汀抑制ERK信号通路有关。