Preparation and in vitro/in vivo evaluation of dextran matrix tablets of budesonide in experimental ulcerative colitis in rats

Budesonide is an anti-inflammatory drug of choice for treatment of ulcerative colitis which affects the rectum and a part of or the entire colon. Delivery of budesonide specifically to the colon would increase the efficacy of the drug and reduce the side-effects. The aim of this study was to develop an oral matrix system formulation for budesonide to deliver the major part of the drug to the colon for treatment of ulcerative colitis that has not been reported before. Directly compressed matrix tablets were prepared using different molecular weights of dextran and three ratios of drug-to-polymer. The physical properties of the tablets including weight variation, hardness, content uniformity, and release profile in HCl 0.1 N, phosphate buffer pH 7.4 and 6.8 containing 4% rat caecal and colonic contents were studied. The efficacy of the desired formulation was also evaluated against acetic acid-induced colitis in rats. Physical properties of the tablets were in the ranges recommended by official references. More than 10% of the drug was released in HCl 0.1 N and pH 7.4, while a very drastic increase was observed after exposure to pH 6.8 containing rat caecal contents. The efficacy of the selected formulation against rat-induced colitis was also increased in comparison to the non-targeted formulation of budesonide. In conclusion, matrix tablets with a 1:10 drug-to-dextran ratio with high molecular weight could deliver the drug specifically to the colon and are promising for treatment of ulcerative colitis.     

极低频率电磁场对小鼠生育能力及着床前期子宫内膜和输卵管上皮细胞高度的影响

目的：探讨极低频率电磁场（extremely low—frequency electromagnetic field,ELF—EMF）对小鼠生育力和着床前期子宫与输卵管上皮细胞高度的影响。方法：80只雌性NMRI小鼠随机分为对照组和EMF组。对照组小鼠不接受EMF,EMF组小鼠接受50Hz、0．5mTEMF,每次4h,每周6次,连续2周。雌小鼠注射孕马血清促性腺激素和人绒毛膜促性腺激素促其排卵,与雄鼠交配。通过观察阴道栓形成确定小鼠妊娠后,冲洗子宫腔获得胚泡,取子宫角和输卵管组织用于光学显微镜检查。结果：EMF组小鼠平均胚泡数比对照组明显减少（P〈0．03）。光学显微镜下观察发现。EMF组小鼠输卵管上皮细胞高度较对照组明显增加,而子宫内膜上皮细胞高度与对照组比较差异无统计学意义。结论：ELF—EMF可能通过减少胚泡数目,增加输卵管上皮细胞高度而损伤雌性小鼠生育能力。     

Characterization, blood profile and biodistribution properties of surface modified PLGA nanoparticles of SN-38

SN-38, the active metabolite of irinotecan, poses a challenge in terms of drug delivery due to its low solubility and labile lactone ring. The aim of this study was to develop a SN-38 nanoparticulate delivery system to evaluate the in vivo blood profile and biodistribution properties of nanoparticles (NPs). Poly lactide-co-glycolide (PLGA) NPs that were covalently bound to polyethylene glycol-folate (PEG-FOL) were prepared, and their in vivo biodistribution in rats was investigated. Either the SN-38 solution or SN-38 NP suspension was administered intravenously into the tail vein at a dose of 2mg SN-38 eq./kg. As expected, SN-38 NPs showed a higher plasma concentration in vivo when compared with free SN-38 during a 24h period. Compared with the SN-38 solution, both folate targeted and non-targeted NPs exhibited superior drug concentration in body organs such as the liver, spleen, and lung at 1 and 8h post-administration.     

Farnesiferol A from Ferula persica and galbanic acid from Ferula szowitsiana inhibit P-glycoprotein-mediated rhodamine efflux in breast cancer cell lines

In multidrug resistance (MDR), cancer cells exposed to anticancer agents develop resistance to a wide variety of chemicals and chemotherapeutic agents. Sesquiterpene coumarins are reported to inhibit P-glycoprotein and/or increase cytotoxicity of anticancer drugs in P-gp-overexpressing cell lines. In the current study, we investigated the effects of galbanic acid (from the roots of Ferula szowitsiana) and farnesiferol A (from the roots of Ferula persica) on functionality of the drug transporter P-glycoprotein (P-gp) using a rhodamine 123 efflux assay in a doxorubicin resistant breast cancer cell line (MCF7/Adr). Compared to verapamil, the well-known inhibitor of P-gp, galbanic acid (5, 10, and 25 μg/mL), significantly inhibited the P-gp activity. In inhibition of the P-gp transporter, farnesiferol A (0.5?μg/mL) was more potent than verapamil at 15 min exposure. Our results indicate that the plant derived sesquiterpene coumarins, farnesiferol A and galbanic acid, may be promising candidates to be considered for further studies on the reversal of multidrug resistance phenotype in chemotherapy of cancer patients.     

Reducing sodium in foods: the effect on flavor

Sodium is an essential micronutrient and, via salt taste, appetitive. High consumption of sodium is, however, related to negative health effects such as hypertension, cardiovascular diseases and stroke. In industrialized countries, about 75% of sodium in the diet comes from manufactured foods and foods eaten away from home. Reducing sodium in processed foods will be, however, challenging due to sodium's specific functionality in terms of flavor and associated palatability of foods (i.e., increase of saltiness, reduction of bitterness, enhancement of sweetness and other congruent flavors). The current review discusses the sensory role of sodium in food, determinants of salt taste perception and a variety of strategies, such as sodium replacers (i.e., potassium salts) and gradual reduction of sodium, to decrease sodium in processed foods while maintaining palatability.     

Interleukin-1 beta and tumor necrosis factor-alpha increase ABCG2 expression in MCF-7 breast carcinoma cell line and its mitoxantrone-resistant derivative, MCF-7/MX

Objective  

In this study, we aimed to evaluate the influence of proinflammatory cytokines on ABCG2 expression and function in human MCF-7 breast cancer cell line and its mitoxantrone-resistant derivative MCF-7/MX.     

Isochaihulactone analogues: synthesis and anti-proliferative activity of novel dibenzylbutyrolactones

A series of dibenzyl-γ-butyrolactones bearing a hydroxyl group at the benzylic position of 3-benzyl group were synthesized as hydrated analogue of isochaihulactone and evaluated against breast cancer human cell lines (MDA-M231, MCF-7 and T47D). The target compounds were synthesized in 7 steps from known lactone; (S)-(+)-γ-benzyloxymethyl-γ-butyrolactone. The key step was the aldol condensation between (+)-(R)-β-(benzo[d][1,3]dioxol-5-ylmethyl)-γ-butyrolactone and substituted benzaldehydes which afforded corresponding α-hydroxybenzyl butyrolactone analogues. The cytotoxic study of the synthesized compounds against breast cancer human cell lines showed that some of them inhibit breast cancer human cell proliferation with percentage inhibitions over 50% at concentrations less than 50?μg/mL.     

Reducing chemotherapy use in clinically high-risk,genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective,randomised phase 3 West German Study Group (WSG) PlanB trial

Purpose

To determine whether BPE in preoperative breast MRI influences patients’ recurrence-free survival (RFS).

Methods

Between February 2010 and December 2011, 804 consecutive women with invasive breast cancer who had undergone preoperative breast MRI and curative cancer surgery were identified. BPE was visually graded by two reviewers. We determined the correlation between BPE grade and other clinicopathological variables, including age, adjuvant therapy, menopausal status, histologic grade, T stage, N stage, lymphovascular invasion, molecular subtype, surgical margin status, and mammographic density. A Cox proportional hazards model was used to analyze the effects of clinicopathological variables and radiological findings (BPE grade, mammographic density) on RFS.

Results

High BPE was associated with premenopausal status (Ps < 0.0001), higher mammographic density (Ps < 0.0001), progesterone receptor positivity (Ps = 0.039, 0.007, respectively), presence of lymphovascular invasion (Ps = 0.008, 0.001, respectively), and close surgical margin (Ps < 0.0001). Recurrences were observed in 75 patients after a mean follow-up period of 61.8 months (range 4–81 months). Non-minimal BPE grade (RFS hazard ratio = 3.086, P = 0.003 for reader 1; RFS hazard ratio = 2.221, P = 0.075 for reader 2) and T3 stage were associated with worse outcomes in postmenopausal women. In premenopausal women, non-minimal BPE grade by readers 1 and 2 did not affect the patients’ outcomes.

Conclusions

Increased BPE on preoperative breast MRI in postmenopausal women has potential as a predictor of poor RFS.