EFFECT OF GROWTH FACTORS ON DNA LABELING AND CYTOSKELETAL PROTEIN EXPRESSION IN 17-β-ESTRADIOL AND BASIC FIBROBLAST GROWTH FACTOR PRE-TREATED ASTROCYTE CULTURES

Astrocytes react to all noxae which damage neurons. Their reactions include degeneration, hypertrophy, hyperplasia and fibre formation. Growth factors inducing proliferation and differentiation of both neurons and astrocytes in culture play a pivotal role in the dynamic flow of signaling molecules between neurons and astroglia. Estrogens as well influence astroglia and are neuroprotectants. This study has investigated the interactions between growth factors and estrogens on DNA labeling and cytoskeletal protein [glial fibrillary acidic protein (GFAP) and vimentin] expression in 22 DIV astrocyte cultures treated for 24 or 36?h under different experimental conditions.

Contemporary addition of 17-β-estradiol (E₂) with two or three growth factors for 24?h, significantly stimulated methyl-[³H]thymidine incorporation into DNA from 22 days in vitro (DIV) astrocyte cultures.

This effect reached a peak when E₂ was co-added with epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and insulin. In astrocyte cultures treated for 36?h with E₂ and EGF+insulin or bFGF+insulin added in the last 12?h, DNA labeling was remarkably increased. The parallel cyclin D1 expression positively correlated with ERK2 activation. Western blot analysis for cytoskeletal proteins showed also changes of both GFAP and vimentin expression. The above data suggest the occurrence of a scheduled interaction between “competence” or “progression” growth factors and estrogens on DNA labeling and cytoskeletal protein expression during astroglial cell proliferation and differentiation in culture. A better understanding of the mechanisms of these interactions may contribute to develop strategies for controlling astroglial reaction in cerebrovascular disease including stroke and hypertensive brain damage.     

Long-term adherence of patients with relapsing-remitting multiple sclerosis to subcutaneous self-injections of interferon β-1a using an electronic device: the RIVER study

ABSTRACT

Objectives: The BRIDGE study has previously shown a high short-term (12 weeks) adherence rate (>85%) of patients with relapsing-remitting multiple sclerosis (RRMS) to subcutaneous self-injections of interferon β-1a using an electronic auto-injection device (RebiSmart®). The primary goal of the RIVER study was to investigate in a real-life setting the long-term adherence to the use of RebiSmart among patients enrolled in the parent BRIDGE study.

Methods: The RIVER study was designed as a real-life extension study of the BRIDGE trial. RRMS patients who completed BRIDGE and still had an indication for treatment were included. Data were collected prospectively through the RebiSmart device, and analyzed retrospectively. Long term adherence (administration of ≥ 80% of injections) to and safety of RebiSmart were assessed. The expected follow-up period ranged from 19 to 26 months.

Results: A total of 57 RRMS patients participated in the follow-up study. The mean observation period was 20.5 ± 5.7 months. The overall adherence to the use of RebiSmart in the entire study cohort was 79.8% (median = 85.2%, range = 16–100%). There were 36 patients (63.2%) who completed at least 80% of the scheduled injections. No statistically significant differences were found between adherent and non-adherent patients in terms of age, sex, duration of the observation period, and occurrence of relapses. No serious treatment-related adverse events occurred.

Conclusions: This study showed a high level of long-term adherence to the use of RebiSmart, with 63.2% of participants meeting the criterion for adherence to treatment.     

17-β雌二醇对宫颈癌Hela细胞环氧合酶-2和增殖细胞核抗原表达的影响

目的:探讨17-β雌二醇(E2)对宫颈癌Hela细胞环氧合酶-2(cyclooxygenase-2,COX-2)和增殖细胞核抗原(proliferatingcell nuclear antigen,PCNA)表达的影响。方法:Hela细胞分别用0.1%乙醇(对照组)、E2(E2组)、E2+依托昔布(E2+依托昔布组)作用24 h后,采用免疫细胞化学、Western blot及RT-PCR方法检测COX-2和PCNA的表达。结果:E2组COX-2和PCNA蛋白及mRNA水平较对照组明显升高(P0.01);而E2+依托昔布组PCNA水平较E2组显著降低(P0.01),但依然高于对照组。结论:E2可促进Hela细胞COX-2表达,并进一步上调PCNA水平。     

Glucagon-like Peptide 1 (7-36 hide) Secretion in Response to Luminal Sucrose from the Upper and Lower Gut: A Study Using α-Glucosidase Inhibition (Acarbose)

Background: After nutrient ingestion there is an early response of glucagon-like peptide 1 (GLP-1) immunoreactivity, although GLP-1 is mainly produced in endocrine cells from the lower gut (ileum and colon/rectum), suggesting that indirect stimulation is important after the ingestion of carbohydrates that are predominantly absorbed from the upper intestine.

Methods: To enable contact of sucrose with lower gut mucosa, sucrose was administered by mouth with and without the simultaneous ingestion of 100mg of the α-glucosidase inhibitor acarbose to six normal healthy volunteers.

Results: There was an early increment in GLP-1 15min after sucrose ingestion. With acarbose, sucrose reached the colon approximately 120min after ingestion, as indicated by an increment in breath hydrogen exhalation (p < 0.0001), and GLP-1 release was prolonged (p < 0.0001). The sucrose-related increments in glucose, insulin, C-peptide, and gastric inhibitory polypeptide (GIP) and the suppression of glucagon were only marginally affected by acarbose administration.

Conclusions: GLP-1 release appears to be influenced by indirect mechanisms (early response after sucrose) and by direct luminal contact with lower gut mucosal endocrine cells (late response with acarbose).     

Improvement of Oral Bioavailability and Anti-Tumor Effect of Zingerone Self-Microemulsion Drug Delivery System

This study sought to prepare a self-microemulsion drug delivery system containing zingerone (Z-SMEDDS) to improve the low oral bioavailability of zingerone and anti-tumor effect. Z-SMEDDS was characterized by particle size, zeta potential and encapsulation efficiency, while its pharmacokinetics and anti-tumor effects were also evaluated. Z-SMEDDS had stable physicochemical properties, including average particle size of 17.29 ± 0.07 nm, the zeta potential of -22.81 ± 0.29 mV, and the encapsulation efficiency of 97.96% ± 0.02%. In vitro release studies have shown the release of zingerone released by Z-SMEDDS was significantly higher than free zingerone in different release media. The relative oral bioavailability of Z-SMEDDS was 7.63 times compared with free drug. Meanwhile, the half inhibitory concentration （IC50）of Z-SMEDDS and free zingerone was 8.45 μg/mL and 13.30 μg/mL, respectively on HepG2. This study may provide a preliminary basis for further clinical research and application of Z-SMEDDS.     

MDR-selective microbial-based therapy: A novel approach to cancer treatment

Microbial-based therapy of cancer is one of the earliest non-surgical anticancer therapies. The main limitation of such therapies is the toxicity of the therapeutic dose. This article discusses a novel approach that exploits cancer multidrug resistance (MDR) to provide a safer microbial-based therapy. As multidrug resistant cells can only contain limited amounts of a variety of susceptible drugs including certain antibiotics, we can take advantage of MDR to create a micro-environment (antibiotic free) that favors growth of intracellular bacteria within cancer cells. Thus, this approach targets cancer cells and spares normal cells (shielded by antibiotic): providing a more selective thus safer anticancer treatment. This article also explores the potentials of Chlamydia pneumoniae as an anti-cancer agent in this MDR-selective microbial-based therapy: its unique life cycle and the immune response to its infection suggest that it could be used directly, in the proposed approach, without any pre-requirements.     

微波联合宫颈炎康栓治愈重度宫颈糜烂206例临床观察和体会

目的观察微波治疗重度宫颈糜烂的全过程，了解术后阴道出血的原因及采用中成药宫颈炎康栓在微波治疗术后对未愈面行局部用药的效果。方法对206例重度宫颈糜烂患者先行微波治疗，2个月后复查，对未痊愈的分别根据患者意愿选择行微波再次手术，或使用宫颈炎康栓局部用药治疗。结果微波治疗206例重度宫颈糜烂患者，一次性治愈率达50．5％，好转率为49．5％，有效率为100％，但术后出现阴道出血率达85％，采用宫颈炎康栓局部用药患者52例，3个疗程治愈率为92．3％，有效率达100％。结论微波是根治重度宫颈糜烂的有效方法，对一次性未治愈的，可选择再次行微波治疗或选用有效中成药，如宫颈炎康栓，局部用药治疗。