Effects of feeding a diet containing Gymnema sylvestre extract: Attenuating progression of obesity in C57BL/6J mice

Objective To investigate the effect of Gymnema sylvestre extract (GS) on initial anti-obesity, liver injury, and glucose homeostasis induced by a high-fat diet (HFD). Methods The dry powder of GS was extracted with methanol, and gymnemic acid was identified by high performance liquid chromatography as deacyl gymnemic acid. Male C57BL/6J mice that fed on either a normal diet, normal diet containing 1 g/kg GS (CON+GS), HFD, or HFD containing 1.0 g/kg GS (HFD + GS) for 4 weeks were used to test the initial anti-obesity effect of GS. Body weight gain and food intake, and serum levels about lipid and liver injury markers were measured. Histopathology of adipose tissue and liver stained with hematoxylin and eosin (H&E) and oil-red O were analyzed. After 4 weeks of GS extract feeding, intraperitoneal glucose tolerance test (IPGTT) was performed. Results The methanol extracts of GS exerted significant anti-obesity effects in HFD + GS group. They decreased body weight gain, a lower food and energy efficiency ratio, and showed lower serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL)-cholesterol, very-low density lipoprotein (VLDL)-cholesterol and leptin compared with the HFD group. The decreases of abdominal as well as epididymal fat weight and adipocyte hypertrophy, lipid droplets in liver, and serum levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) were also observed. The CON + GS group showed an effect of glucose homeostasis compared to the CON group. Conclusions This study shows that GS provide the possibility as a key role in an initial anti-obesity effects feeding with a HFD.

Effects of feeding a diet containing Gymnema sylvestre extract: Attenuating progression of obesity in C57BL/6J mice

OBJECTIVE@#To investigate the effect of Gymnema sylvestre extract (GS) on initial anti-obesity, liver injury, and glucose homeostasis induced by a high-fat diet (HFD).@*METHODS@#The dry powder of GS was extracted with methanol, and gymnemic acid was identified by high performance liquid chromatography as deacyl gymnemic acid. Male C57BL/6J mice that fed on either a normal diet, normal diet containing 1 g/kg GS (CON+GS), HFD, or HFD containing 1.0 g/kg GS (HFD + GS) for 4 weeks were used to test the initial anti-obesity effect of GS. Body weight gain and food intake, and serum levels about lipid and liver injury markers were measured. Histopathology of adipose tissue and liver stained with hematoxylin and eosin (H&E) and oil-red O were analyzed. After 4 weeks of GS extract feeding, intraperitoneal glucose tolerance test (IPGTT) was performed.@*RESULTS@#The methanol extracts of GS exerted significant anti-obesity effects in HFD + GS group. They decreased body weight gain, a lower food and energy efficiency ratio, and showed lower serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL)-cholesterol, very-low density lipoprotein (VLDL)-cholesterol and leptin compared with the HFD group. The decreases of abdominal as well as epididymal fat weight and adipocyte hypertrophy, lipid droplets in liver, and serum levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) were also observed. The CON + GS group showed an effect of glucose homeostasis compared to the CON group.@*CONCLUSIONS@#This study shows that GS provide the possibility as a key role in an initial anti-obesity effects feeding with a HFD.

Acute Pulmonary Toxicity and Body Distribution of Inhaled Metallic Silver Nanoparticles

The purpose of this study was to determine the acute pulmonary toxicity of metallic silver nanoparticles (MSNPs, 20.30 nm in diameter). Acute pulmonary toxicity and body distribution of inhaled MSNPs in mice were evaluated using a nose-only exposure chamber (NOEC) system. Bronchoalveolar lavage (BAL) fluid analysis, Western blotting, histopathological changes, and silver burdens in various organs were determined in mice. Mice were exposed to MSNPs for 6 hrs. The mean concentration, total surface area, volume and mass concentrations in the NOEC were maintained at 1.93 x 10(7) particles/cm3, 1.09 x 10(10) nm2/cm3, 2.72 x 10(11) nm3/cm3, and 2854.62 microg/m3, respectively. Inhalation of MSPNs caused mild pulmonary toxicity with distribution of silver in various organs but the silver burdens decreased rapidly at 24-hrs post-exposure in the lung. Furthermore, inhaled MSNPs induced activation of mitogen-activated protein kinase (MAPK) signaling in the lung. In summary, single inhaled MSNPs caused mild pulmonary toxicity, which was associated with activated MAPK signaling. Taken together, our results suggest that the inhalation toxicity of MSNPs should be carefully considered at the molecular level.

Aerosol delivery of kinase-deficient Akt1 attenuates Clara cell injury induced by naphthalene in the lungs of dual luciferase mice

Conventional lung cancer therapies are associated with poor survival rates; therefore, new approaches such as gene therapy are required for treating cancer. Gene therapies for treating lung cancer patients can involve several approaches. Among these, aerosol gene delivery is a potentially more effective approach. In this study, Akt1 kinase-deficient (KD) and wild-type (WT) Akt1 were delivered to the lungs of CMV-LucR-cMyc-IRES-LucF dual reporter mice through a nose only inhalation system using glucosylated polyethylenimine and naphthalene was administrated to the mice via intraperitoneal injection. Aerosol delivery of Akt1 WT and naphthalene treatment increased protein levels of downstream substrates of Akt signaling pathway while aerosol delivery of Akt1 KD did not. Our results showed that naphthalene affected extracellular signal-regulated kinase (ERK) protein levels, ERK-related signaling, and induced Clara cell injury. However, Clara cell injury induced by naphthalene was considerably attenuated in mice exposed to Akt1 KD. Furthermore, a dual luciferase activity assay showed that aerosol delivery of Akt1 WT and naphthalene treatment enhanced cap-dependent protein translation, while reduced cap-dependent protein translation was observed after delivering Akt1 KD. These studies demonstrated that our aerosol delivery is compatible for in vivo gene delivery.

Low dietary inorganic phosphate affects the lung growth of developing mice

Inorganic phosphate (Pi) plays a critical role in diverse cellular functions, and regulating the Pi balance is accomplished by sodium-dependent Pi co-transporter (NPT). Pulmonary NPT has recently been identified in mammalian lungs. However, to date, many of the studies that have involved Pi have mainly focused on its effect on bone and kidney. Therefore, current study was performed to discover the potential effects of low Pi on the lung of developing transgenic mice expressing the renilla/firefly luciferase dual reporter gene. Two-weeks old male mice divided into 2 groups and these groups were fed either a low PI diet or a normal control diet (normal: 0.5% Pi, low: 0.1% Pi) for 4 weeks. After 4 weeks of the diet, all the mice were sacrificed. Their lungs were harvested and analyzed by performing luciferase assay, Western blotting, kinase assay and immunohistochemistry. Our results demonstrate that low Pi affects the lungs of developing mice by disturbing protein translation, the cell cycle and the expression of fibroblast growth factor-2. These results suggest that optimally regulating Pi consumption may be important to maintain health.

Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells.

A Gap Analysis between Inpatients' and Personnel's Perception of Hospital Foodservice Quality / 대한지역사회영양학회지

The purposes of this study were to analyze the gap between foodservice personnel and inpatients, to urge foodservice providers to reconsider by identifying the problems in service delivery for customer satisfaction, and to deduce the priority for foodservice quality improvement. The results of this study can be summarized as follows : the average perception score of personnel (4.32 out of 5) was higher than that of customers (3.90). In particular, the customers' perceptions of 17 attributes, which included 'removal service of tray by foodservice personnel', 'nutrition and health-related information service', 'handling inpatient's complaint ASAP', 'delicious meals' and 'salty enough meals' and so on, was significantly lower than personnel's. Both service providers and customers perceived that 'personnel attitude' was the highest and 'meal quality' was the lowest among the 4 factors, but there was significant difference on 'meal quality' (p<.001), 'customer reception' (p<.001) and 'personnel attitude' (p<.05) between the two groups. As a results of quadrant analysis, 'removal service of tray by foodservice personnel', 'handling inpatient's complaints ASAP' and 'meal service according to doctor's orders were categorized into Quadrant A with meaning of high personnel's perceptions and low customers'. Therefore service providers have to perceive the gap between the two viewpoints and grant priority to these attributes in improving foodservice quality.

Development of Quality Assessment Tool and Application to Customer-Oriented Hospital Foodservice Management

The purposes of this study were to : a) develop the quality assessment tool of hospital foodservice management, b) evaluate the S hospital's foodservice quality by this tool, and c) do the feasibility study about this tool in hospital foodservice field by establishing quality management strategies. The developed quality assessment tool of hospital foodservice management was consisted of 20 items for quality evaluation by Likert 5 point scale and two additional questions with the most satisfactory item and the most unsatisfactory item. As a result of evaluation, S hospital's foodservice quality was somewhat high, on the factor 'personnel attitude', especially. The IPA technique proved nine items including Q5, Q7, Q8, Q11, Q12, Q13, Q15, Q16, Q17 were in 'Doing Great, Keep It Up' and seven items such as Q1, Q2, Q3, Q6, Q9, Q18, Q19 that got high expectation and low perception needed to be focused in quality management strategy.

Evaluation of Foodservice Quality on the Viewpoint of Personnel in Hospital Foodservice

The purposes of this study was to evaluate the foodservice quality on the viewpoint of personnel in hospital foodservice. In result, S hospital's foodservice quality, that was evaluated by personnel, was comparatively high on the every variables and factors, especially on 'Q13. Meals delivery to the bed'(4.70 out of 5.0), 'Q14. Removal service of tray by foodservice personnel'(4.63), 'Q15. Kind foodservice personnel'(4.63), 'Q16. Foodservice personnel's clean and neat uniforms'(4.56) and 'factor 4. personnel attitude'(4.63). Foodservice quality factors weren't significant by general characteristics of personnel, thus all personnel were considered to hold similarly the level of foodservice quality. On the basis of these results, the gap between foodservice providers and customers need to be analyzed in the further study.

The Radioprotective Effect and Mechanism of Captopril on Radiation Induced-Heart Damage in Rats / 대한방사선종양학회지

PURPOSE: Captopril (angiotension converting enzyme inhibitor) is known to have a radioprotective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotective effect and mechanism of captopril in the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats. MATERIALS AND METHODS: The histopathological changes and immunohistochemical stains (TNF alpha, TGFbeta1, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment. RESULTS: In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema (p=0.082) and fibrin deposit (p=0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit (p=0.047) in the atrium, and the interstitial fibrin deposit (p=0.019) and edema (p=0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of TNF-alpha, TGF-beta1, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial TNF-alpha and TGF-beta1 in the radiation alone group continuously increased. The expressions of TNF-alpha, TGF-beta1 and PDGF were decreased in the combined group at 2 weeks. At 8 weeks, the expressions of TNF-alpha in the atrial and ventricular pericardia were markedly reduced (p=0.049, p=0.009). CONCLUSIONS: This study revealed that the early heart damage induced by radiation can be reduced by the addition of captopril in a rat model. The expressions of TNF-alpha, TGF-beta1 and PDGF were further decreased in the combined compared to the radiation alone group at both 2 and 8 weeks. From these results, it may be concluded that these cytokines probably play roles in the radioprotective mechanism of captopril from the radiation-induced heart toxicity, similarly to in other organs.

B6C3F1 mice exposed to ozone with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and/or dibutyl phthalate showed toxicities through alterations of NF-kappaB, AP-1, Nrf2, and osteopontin

Toxic effects of ozone, 4-(N-methyl-N-nitrosamino)-1-(3- pyridyl)-1-butanone (NNK), and/or dibutyl phthalate (DBP) were examined through NF-kappaB, AP-1, Nrf2, and osteopontin (OPN) in lungs and livers of B6C3F1 mice. Electrophoretic mobility shift assay (EMSA) indicated that mice treated with combination of toxicants induced high NF-kappaB activities. Expression levels of p105, p65, and p50 proteins increased in all treated mice, whereas IkB activity was inhibited in NNK-, DBP-, and combination-treated ones. All treated mice except ozone-treated one showed high AP-1 binding activities. Expression levels of c-fos, c-jun, junB, jun D, Nrf2, and OPN proteins increased in all treated mice. Additive interactions were frequently noted from two-toxicant combination mice compared to ozone-treated one. These results indicate treatment of mixture of toxicants increased toxicity through NF-kappaB, AP-1, Nrf2, and OPN. Our data could be applied to the elucidation of mechanism as well as the risk assessment of mixture-induced toxicity.

Radiation Oncology Digital Image Chart and Digital Radiotherapy Record System at Samsung Medical Center / 대한방사선종양학회지

BACKGROUND: The authors have developed a Digital image chart(DIC) and digital Radiotherapy Record System (DRRS). We have evaluated the DIC and DRRS for reliability, usefulness, ease of use, and efficiency. METHOD AND MATERIALS: The basic design o f the DIC and DRRS was to build an digital image database of radiation therapy patient records for a more efficient and timely flow of critical image in formation throughout the department. This system is a subunit of comprehensive radiation oncology managemert system (C-ROMS) and composed of a picture archiving and communication system (PACS), radiotherapy information database, and a radiotherapy imaging database. The DIC and DRRS were programmed using Delphi under a Windows 95 environment and is capable of displaying the digital images of patients identification photos, simulation films, radiotherapy setup, diagnostic radiology image... Gross lesion photos, and radiotherapy planning isodose charts with beam arrangements. Twenty-three clients in the department are connected by Ethernet (10 Mbps) to the central image server (Sun Ultra-sparc 1 workstation). RESULTS: From the introduction of this system in February 1998 through December 1999, we have accumulated a total of 15,732 individual images for 2,556 patients. We can organize radiation therapy in; paperless environment in 120 patients with breast cancer. Using this system, we have succeeded in the prompt, accurate, and simultaneous access to patient care information from multiple locations throughout the department. This coordination has resulted in improved operational efficiency within the department. CONCLUSION: The authors believe that the DIC and DRRS has contributed to the improvement of radiation oncology department efficacy as well as to time and resource savings by providing necessary visual information throughout the department conveniently and simultaneously. As a result, we can also achieve the paperless and filmless practice of radiation oncology with this system.

Dose-Response Relationship of Radiotherapy for Locally Advanced Hepatocellular Carcinoma / 대한암학회지

PURPOSE: Recently radiotherapy is applied alone or in conjunction with transcatheter arterial chemoembolizaion (TACE) or percutaneous ethanol injection therapy (PEIT) for locally advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate dose-response relationship of radiotherapy for local control and toxicity in inoperable HCC. MATERIALS AND METHODS: Twenty-eight patients who were not eligible for TACE and PEIT or had showed no response to these treatment were treated with a total dose of 40 Gy with 2 Gy per fraction or 30 Gy with 3 Gy per fraction (low dose group, 18 patients) or 45 Gy with 3 Gy per fraction (high dose group, 10 patients). RESULTS: The median survival duration was 8 months and 1-year survival rate was 37%. The treatment results were as follows; partial response in 11% and 70% (p=0.001), stable disease in 56% and 30%, and progressive disease in 33% and 0% in low dose group and high dose group, respectively. The incidence of gastrointestinal (G-I) toxicity by the criteria of Southwest Oncology Group was as follows; grade 1 in 22% and 40%, grade 2 in 17% and 10%, respectively (p=0.56). There was no patient with severe G-I toxicity above grade 3. The incidence of G-I toxicity by site was as follows; grade 1 in 24% and 29%, and grade 2 in 0% and 57% in patients with right lobe and left lobe lesion, respectively (p=0.001). CONCLUSION: This study indicates that there is clear dose-response relationship in local control. The G-I toxicity does not increase significantly with increment of radiation dose within the dose range tested in this study. And careful attention should be paid for G-I toxicity when the tumor is located in left lobe.

Preliminary Results of Postoperative Radiotherapy after Breast Conserving Surgery in Early Breast Cancer / 대한암학회지

PURPOSE: To evaluate treatment results of breast conserving surgery and radiation therapy including survival rates, patterns of failure, and complication and to analyze prognostic factors. MATERIALS AND METHODS: Retrospective analysis was carried out for 111 (112 cases) consecutive patients with breast cancer treated by radiation therapy after breast conserving surgery from October 1994 to April 1997. The median follow up was 45 months (range 10~66). AJCC staging was as follows: 16 cases (14%) for ductal carcinoma in situ, 46 cases (41%) for stage I, 33 cases (30%) for stage IIa, and 17 cases (15%) for stage IIb. Radiation therapy after breast conserving surgery was delivered to whole breast with 50.4 Gy and additional 10 Gy electron beam boost to tumor bed. Adjuvant CMF or CAF chemotherapy was performed in 61 patients. RESULTS: Overall three- and five-year survivals were 99% and 95%, and progression-free survival were 93%, 87%, respectively. Treatment failure occurred in 11 cases (10%); loco-regional recur rence in six; distant metastasis in five. Univariate analysis showed prognostic factor affecting survival was only T-stage. Acute radiation dermatitis were found in five cases (4%), and chronic complications were found in five (4%); one case with amputation of nipple, two cases with lymphedema requiring rehabilitation therapy and two cases with symptomatic radiation pneu monitis requiring steroid therapy. CONCLUSION: Breast conserving therapy of early breast cancer including ductal carcinoma in situ showed high survival rates and low complications, and T stage was prognostic factor for survival. But further follow-up should be needed.

The Results of Definitive Radiation Therapy and The Analysis of Prognostic Factors for Non-Small Cell Lung Cancer / 대한방사선종양학회지

PURPOSE: This retrospective study was tried to evaluate the clinical characteristics of patients, patterns of failure, survival rates, prognostic factors affecting survival, and treatment related toxicities when non-small cell lung cancer patients was treated by definitive radiotherapy alone or combined with chemotherapy. MATERIAL AND METHODS: We evaluated the treatment results of 70 patients who were treated by definitive radiation therapy for non-small cell lung cancer at the Department of Radiation Oncology, Ewha Womans University Hospital, between March 1982 and April 1996. The number of patients of each stage was 2 in stage I, 6 in stage II, 30 in stage III-A, 29 in stage III- B, 3 in stage IV. Radiation therapy was administered by 6 MV linear accelerator and daily dose was 1.8-2.0 Gy and total radiation dose was ranged from 50.4 Gy to 72.0 Gy with median dose 59.4 Gy. Thirty four patients was treated with combined therapy with neoadjuvant or concurrent chemotherapy and radiotherapy, and most of them were administered with the multi-drug combined chemotherapy including etoposide and cisplatin. The survival rate was calculated with the Kaplan-Meier methods. RESULTS: The overall 1-year, 2-year, and 3-year survival rates were 63%, 29%, and 26%, respectively. The median survival time of all patients was 17 months. The disease-free survival rate for 1-year and 2-year were 23% and 16%, respectively. The overall 1-year survival rates according to the stage was 100% for stage I, 80% for stage II, 61% for stage III, and 50% for stage IV. The overall 1-year, 2-year, and 3-year survival rates for stage III patients only were 61%, 23%, and 20%, respectively. The median survival time of stage III patients only was 15 months. The complete response rates by radiation therapy was 16% and partial response rate was 50%. Thirty patients (43%) among 70 patients assessed local control at initial 3 months follow-up duration. Twenty four (80%) of these 30 patients was possible to evaluate the pattern of failure after achievement of local control. And then, treatment failure occured in 14 patients (58%); local relapse in 6 patients (43%), distant metastasis in 6 patients (43%) and local relapse with distant metastasis in 2 patients (14%). Therefore, 16 patients (23%) were controlled of disease of primary site with or without distant metastases. Twenty three patients (46%) among 50 patients who were possible to follow-up had distant metastasis. The overall 1-year survival rate according to the treatment modalities was 59% in radiotherapy alone and 66% in chemoirradiation group. The overall 1-year survival rates for stage III patients only was 51% in radiotherapy alone and 68% in chemoirradiation group which was significant different. The significant prognostic factors affecting survival rate were the stage and the achievement of local control for all patients at univariate- analysis. Use of neoadjuvant or concurrent chemotherapy, use of chemotherapy and the achievement of local control for stage III patients only were also prognostic factors. The stage, pretreatment performance status, use of neoadjuvant or concurrent chemotherapy, total radiation dose and the achievement of local control were significant at multivariate analysis. The treatment-related toxicities were esophagitis, radiation pneumonitis, hematologic toxicity and dermatitis, which were spontaneously improved, but 2 patients were died with radiation pneumonitis. CONCLUSION: The conventional radiation therapy was not sufficient therapy for achievement of long-term survival in locally advanced non-small cell lung cancer. Therefore, aggressive treatment including the addition of appropriate chemotherapeutic drug to decrease distant metastasis and preoperative radiotherapy combined with surgery, hyperfractionation radiotherapy or 3-D conformal radiation therapy for increase local control are needed.

The Effect of Irradiation and Cis-diamminedichloroplatinum (II) in the Rat Brain : Analysis of Histopathology at 3 and 6 Months after Treatment / 대한방사선종양학회지

PURPOSE: To evalute the late effect (3 and 6 months) of cis-diamminedichloroplatinum (II) (cisplatin) on the radiation brain damage when the cisplatin was intraperitoneally infused immediately after whole brain irradiation in the rats. MATERIALS AND METHODS: The histolopathological findings of the brain were examined in rat brains at 3 and 6 months after the treatment. The rats were irradiated (20 or 22.5 Gy, RT) or cisplatin was injected intraperitoneally (2, 4, or 8mg/kg, CT) and in combined treatment group, cisplatin (2mg/kg) was injected immediately after irradiation (20 or 22.5 Gy). Histopathological examination was done mostly in irradiation or cisplatin alone groups, because the rats in combined group died during experimental period except 2 rats. RESULTS: The rats treated with cisplatin showed marked epithelial vacuolation with perivascular edema and vascular dilatation in choroid plexus at 3 months as well as multifocal necrosis involving fimbria and cerebellar hemispheres at 3 and 6 months. The changes were more prominent in rats with 2mg/kg injection compared to rats with 8mg/kg injection.The rats with RT and combined CT and RT showed characteristic delayed irradiation effects such as focal coagulation necrosis and vascular changes, which were more marked than previous reports. Prominent perivascular and leptomeningeal astrocytic proliferation was well documented by anti-GFAP antibody. Cisplatin treatment did not enhance the effect of radiation-induced changes of blood vessels and astrocytic proliferation. CONCLUSION: The focal necrosis was the most consistently noted finding in this study, it suggested the possibility to use this as an evaluation factor for combined effects of RT and cisplatin.

The Effect of Irradiation and Cis-diamminedichloroplatinum (II) in the Rat Brain : Analysis of Histopathology at 3 and 6 Months after Treatment / 대한방사선종양학회지

PURPOSE: To evalute the late effect (3 and 6 months) of cis-diamminedichloroplatinum (II) (cisplatin) on the radiation brain damage when the cisplatin was intraperitoneally infused immediately after whole brain irradiation in the rats. MATERIALS AND METHODS: The histolopathological findings of the brain were examined in rat brains at 3 and 6 months after the treatment. The rats were irradiated (20 or 22.5 Gy, RT) or cisplatin was injected intraperitoneally (2, 4, or 8mg/kg, CT) and in combined treatment group, cisplatin (2mg/kg) was injected immediately after irradiation (20 or 22.5 Gy). Histopathological examination was done mostly in irradiation or cisplatin alone groups, because the rats in combined group died during experimental period except 2 rats. RESULTS: The rats treated with cisplatin showed marked epithelial vacuolation with perivascular edema and vascular dilatation in choroid plexus at 3 months as well as multifocal necrosis involving fimbria and cerebellar hemispheres at 3 and 6 months. The changes were more prominent in rats with 2mg/kg injection compared to rats with 8mg/kg injection.The rats with RT and combined CT and RT showed characteristic delayed irradiation effects such as focal coagulation necrosis and vascular changes, which were more marked than previous reports. Prominent perivascular and leptomeningeal astrocytic proliferation was well documented by anti-GFAP antibody. Cisplatin treatment did not enhance the effect of radiation-induced changes of blood vessels and astrocytic proliferation. CONCLUSION: The focal necrosis was the most consistently noted finding in this study, it suggested the possibility to use this as an evaluation factor for combined effects of RT and cisplatin.