Differential modulation by baclofen on antinociception induced by morphine and beta-endorphin administered intracerebroventricularly in the formalin test

Our previous studies have demonstrated that supraspinal GABAergic receptors are differentially involved in the antinociception induced by morphine and beta-endorphin given intracerebroventricularly (i.c.v.) in the tail-flick and hot-plate tests. These two models employed a phasic, thermal nociceptive stimulus. The present study was designed to examine the possible involvement of supraspinal GABAergic receptors in opioid-induced antinociception in the formalin test. Morphine (1 microg) and beta-endorphin (1 microg) given i.c.v. displayed the almost complete inhibitory effects against the hyperalgesic response in both phases. Muscimol (75-100 ng) and baclofen (5-10 ng) injected i.c.v. produced the hypoalgesic response in the both phases. The hypoalgesic response induced by muscimol and baclofen observed during the second phase was more pronounced than that observed during the second phase. Baclofen (2.5 ng), at the dose which did not affect the hyperalgesic response, resulted in a significant reversal of the i.c.v. administered beta-endorphin-induced hypoalgesic response observed during the second, but not the first, phase. However, the hypoalgesic response induced by i.c.v. administered morphine was not changed by the same dose of muscimol or baclofen injected i.c.v. Our results indicate that, at the supraspinal level, GABA(B)receptors appear to be involved in the modulation of antinociception induced by supraspinally administered beta-endorphin, but not morphine, in the formalin test model.     

Purification and characterization of Moran 20K fromMorus alba

A new glycoprotein was purified from the aqueous methanolic extract of the root bark ofMorus alba which has been used as a component of antidiabetic remedy in Oriental Medicine. SDS-PAGE result shows that the molecular weight of the glycoprotein was approximately 20 kDa. This new glycoprotein was named as Moran 20K. The protein lowered blood glucose level in streptozotocin-induced hyperglycemic mice model and it also increased the glucose transport in cultured epididymis fat cells. The amino acid composition of the protein was analyzed, and the protein contained above 20% serine and cysteine such as insulin. The actual molecular weight of the protein was determined as 21,858 Da by MALDI-TOF mass spectroscopy.     

Effect of melatonin on the regulation of proenkephalin and prodynorphin mRNA levels induced by kainic acid in the rat hippocampus

The in vivo short-term effect of melatonin on kainic acid (KA)-induced proenkephalin (proENK) or prodynorphin (proDYN) mRNA, and on AP-1 protein levels in the rat hippocampus, were studied. Melatonin (5 mg/kg) or saline was administered intraperitoneally (i.p.) to rats 30 min prior to and immediately after i.p. injection of KA (10 mg/kg). Rats were sacrificed 1 and 3 h after KA injection. The proENK and proDYN mRNA levels were significantly increased 3 h after KA administration. The elevations of both proENK and proDYN mRNA levels induced by KA were significantly inhibited by the preadministration with melatonin. The increases of proENK and proDYN mRNA levels induced by KA were well-correlated with the increases of c-Fos, Fra-2, FosB, c-Jun, and JunB protein levels, which were significantly increased 3 h after KA administration and effectively inhibited by administration with melatonin. In an electrophoretic mobility shift assay, both AP-1 and ENKCRE-2 DNA binding activities were increased by KA, which were also attenuated by the administration of melatonin. In addition, cross-competition studies revealed that AP-1 or ENKCRE-2 DNA binding activity was effectively reduced by the 50x unlabeled cross-competitor. Therefore, these data suggest that melatonin has an inhibitory role in KA-induced gene expression, such as proENK and proDYN mRNA expression, and this may be due to a reduction of KA-induced AP-1 or ENKCRE-2 DNA binding activity.     

Interfractional variation in position of the uterus during radical radiotherapy for cervical cancer.

BACKGROUND AND PURPOSE: This study was conducted to investigate the positional change of the uterus during radiotherapy which can degrade the accuracy of three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT). PATIENTS AND METHODS: Sixty-six patients received radical radiotherapy for cervical cancer in Samsung Medical Center. For each patient, two MRI scans were taken; one was before beginning radiotherapy and the other was in the third or fourth week of radiotherapy. In T2-weighted MRI images, the positional change of the uterus was quantified by measuring six parameters; the distance from the external uterine opening to the isthmus of the uterus (Dcx), the distance from the isthmus of the uterus to the uterine fundus (Dco), the perpendicular distance of the uterine body to the uterine corpus (Dco-per), the angle between the vertical line and the cervical canal in sagittal images (Acx), the uterine corpus angle from the vertical line in sagittal plan (Aco), the angle between the uterine corpus from an arbitrary bony landmark and a vertical mid line in axial images (Aco-axi) RESULTS: Mean value of change in Dcx+Dco of tumor size during treatment was 8.0 mm in small tumors and 17.9 mm in large tumors. Among 44 anteflexed uterus patients, 5 changed into a retroflexed position. 12 patients (18%) had a greater than 30 degrees variation in any angle. For patients under 60 years, the difference in Acx was statistically significant. CONCLUSIONS: Positional changes of the uterus during radiotherapy should be considered in the treatment planning of 3DCRT or IMRT, particularly in patients under 60 years or those with tumor size greater than 4 cm in diameter.     

Radiation Therapy Results for Patients Undergoing Inappropriate Surgery in the Presence of Invasive Cervical Carcinoma

Total vaginal or abdominal hysterectomy was considered an inadequate treatment method for invasive uterine cervix cancer. Usually the procedure was inadvertently performed on patients who were thought preoperatively to have benign or premalignant conditions. Between 1985 and 1993, 64 patients undergoing hysterectomy in the presence of invasive cervical cancer were treated with external radiation therapy and/or intracavitary radiotherapy. Preoperative diagnoses were carcinomain situ(36), severe dysplasia (2), and early invasive cancer (14), and others were benign disease. Overall 5-year survival and relapse-free survival rates were 75.8 and 77.5%, respectively. For patients in retrospective stage IA, IB, and IIB (gross residual after surgery), overall 5-year survival rates were 90.9, 88.8, and 27.9%, respectively. Thirteen patients developed treatment failure; most of them (10/13) were patients with gross residual disease. Patients with early invasive cervical cancer (stage IA) had no treatment-related failure. Prognostic factors affecting survival by univariate analysis were retrospective stage (P= 0.0000) and preoperative diagnosis (P= 0.0021). Tumor histology was marginally significant factor (P= 0.0938). By multivariate analysis, only retrospective stage was significant prognostic factor (P= 0.0001). Adjuvant radiotherapy appears to be an effective treatment method for patients with presumed stage IA and IB after inadvertent hysterectomy. Survival for patients with gross disease remaining after inappropriate hysterectomy is poor. So, early cancer detection and proper management with precise pretreatment staging is necessary to avoid inadherent hysterectomy, especially in cases of gross residual disease.     

X-radiation induces 8-hydroxy-2'-deoxyguanosine formation in vivo in rat mammary gland DNA

Ionizing radiation is a carcinogen that induces oxidative DNA damage. 8- Hydroxy-2'-deoxyguanosine (8-OHdG) is a relatively abundant, mutagenic lesion that is widely regarded as a reliable index of oxidative DNA damage. The purpose of this study was to examine the effects of X- radiation on levels of 8-OHdG in the context of an experimental model for breast cancer in which chronic radiation exposure has been shown to be carcinogenic in Sprague-Dawley rats. A secondary objective of this study was to determine if the use of phenol during DNA isolation affected the concentration of 8-OHdG subsequently measured. Our results indicate that a profoundly carcinogenic dose of radiation induced a small but significant increase in 8-OHdG concentration in mammary gland DNA, and that the use of a phenol-based versus a salt-based method of DNA isolation had no significant impact on the levels of 8-OHdG detected in either control or irradiated tissue.      

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.