Radioprotective effects of delphinidin on normal human lung cells against proton beam exposure

BACKGROUND/OBJECTIVES: Exposure of the normal lung tissue around the cancerous tumor during radiotherapy causes serious side effects such as pneumonitis and pulmonary fibrosis. Radioprotectors used during cancer radiotherapy could protect the patient from side effects induced by radiation injury of the normal tissue. Delphinidin has strong antioxidant properties, and it works as the driving force of a radioprotective effect by scavenging radiation-induced reactive oxygen species (ROS). However, no studies have been conducted on the radioprotective effect of delphinidin against high linear energy transfer radiation. Therefore, this study was undertaken to evaluate the radioprotective effects of delphinidin on human lung cells against a proton beam. MATERIALS/METHODS: Normal human lung cells (HEL 299 cells) were used for in vitro experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay assessed the cytotoxicity of delphinidin and cell viability. The expression of radiation induced cellular ROS was measured by the 2′-7′-dicholordihydrofluorescein diacetate assay. Superoxide dismutase activity assay and catalase activity assay were used for evaluating the activity of corresponding enzymes. In addition, radioprotective effects on DNA damage-induced cellular apoptosis were evaluated by Western blot assay. RESULTS: Experimental analysis, including cell survival assay, MTT assay, and Western blot assay, revealed the radioprotective effects of delphinidin. These include restoring the activities of antioxidant enzymes of damaged cells, increase in the levels of pro-survival protein, and decrease of pro-apoptosis proteins. The results from different experiments were compatible with each to provide a substantial conclusion. CONCLUSION: Low concentration (2.5 µM/mL) of delphinidin administration prior to radiation exposure was radioprotective against a low dose of proton beam exposure. Hence, delphinidin is a promising shielding agent against radiation, protecting the normal tissues around a cancerous tumor, which are unintentionally exposed to low doses of radiation during proton therapy.

Therapeutic effects of dihydroartemisinin and transferrin against glioblastoma

BACKGROUND/OBJECTIVES: Artemisinin, a natural product isolated from Gaeddongssuk (artemisia annua L.) and its main active derivative, dihydroartemisinin (DHA), have long been used as antimalarial drugs. Recent studies reported that artemisinin is efficacious for curing diseases, including cancers, and for improving the immune system. Many researchers have shown the therapeutic effects of artemisinin on tumors such as breast cancer, liver cancer and kidney cancer, but there is still insufficient data regarding glioblastoma (GBM). Glioblastoma accounts for 12-15% of brain cancer, and the median survival is less than a year, despite medical treatments such as surgery, radiation therapy, and chemotherapy. In this study, we investigated the anti-cancer effects of DHA and transferrin against glioblastoma (glioblastoma multiforme, GBM). MATERIALS/METHODS: This study was performed through in vitro experiments using C6 cells. The toxicity dependence of DHA and transferrin (TF) on time and concentration was analyzed by MTT assay and cell cycle assay. Observations of cellular morphology were recorded with an optical microscope and color digital camera. The anti-cancer mechanism of DHA and TF against GBM were studied by flow cytometry with Annexin V and caspase 3/7. RESULTS: MTT assay revealed that TF enhanced the cytotoxicity of DHA against C6 cells. An Annexin V immune-precipitation assay showed that the percentages of apoptosis of cells treated with TF, DHA alone, DHA in combination with TF, and the control group were 7.15 ± 4.15%, 34.3 ± 5.15%, 66.42 ± 5.98%, and 1.2 ± 0.15%, respectively. The results of the Annexin V assay were consistent with those of the MTT assay. DHA induced apoptosis in C6 cells through DNA damage, and TF enhanced the effects of DHA. CONCLUSION: The results of this study demonstrated that DHA, the derivative of the active ingredient in Gaeddongssuk, is effective against GBM, apparently via inhibition of cancer cell proliferation by a pharmacological effect. The role of transferrin as an allosteric activator in the GBM therapeutic efficacy of DHA was also confirmed.

Spectral Analysis of Heart Rate Variability Following Endoscopic Thoracic Sympathicotomy / 대한마취과학회지

BACKGROUND: In general, we know that a thoracic sympathicotomy may have influence an cardiac autonomic nervous activity to change vital signs. The purpose of this study was to analyse preoperative and postoperative heart rate variability to evaluate the influence of a sympathicotomy on cardiac autonomic activity. METHODS: We studied 14 healthy patients, ASA physical status I and II, undergoing an endoscopic thoracic sympathicotomy. A laryngeal airway mask was performed on all patients for tracheal intubation. Intravenous anesthesia was induced by administration of propofol 10 mg/kg, and fentanyl 2ng/kg and was maintained with propofol 10ng/kg/hr and N2O-O2 (2 L/min-2 L/min). An electrocardiogram was checked in the supine position with Biopac Student Lab. at an hour before anesthetic induction, after a left and right sympathicotomy and at 3 - 4 hours after emergence. A spike 2 version 3.0 was used for analyzing heart rate variability and a Fast Fourier Transform was used to yield a power spectrum. Frequency bands were divided to low frequency (0.02 - 0.09 Hz), middle frequency (0.1 - 0.15 Hz), and high frequency (0.16 - 1.0 Hz) components. RESULTS: There were no significant changes of heart rate, high frequency component, low frequency component and ratio of low to high frequency component. CONCLUSIONS: Influence of a thoracic sympathicotomy on cardiac autonomic activity was less in the supine position at rest. However, we think that the response of the cardiac autonomic activity to sympathetic stimulation like position change and exercise after a sympathicotomy may yield different results and studies about this must be done.

MR imaging of internuclear ophthalmoplegia due to cerebrovascular diseases / 영남의대학술지

Internuclear ophthalmoplegia is a conjugated gaze disorder characterized by impaired adduction on the side of a lesion involving the medial longitudinal fasciculus with dissociated nystagmus of the other abducting eye. Six patients with INO (who had clinical cerebrovascular diseases) underwent MR imaging and the results were as follows: 1. The MLF lesions were identified by MR imaging in 5 cases 2. The ratio of unilateral INO to bilateral INO was 5:1 3. The nature of lesions was infarction in 4 cases and hemorrhage in 1 case 4. The sites of MLE lesion were in the midbrain in 4 cases and in the pons in 1 case 5. All 5 cases of INO identified by MR imaging had other lesion sites in addition to MLE lesion.

The study on the histopathologic changes in chorioallantoic membrane of the fertilized chicken eggs where the MBT-2 mice bladder cancer and the human bladder cancer tissue were implanted and chemosensitivity test for anticancert drugs / 대한비뇨기과학회지

The MBT-2 mice bladder cancer tissues and the human bladder cancer tissues were implanted on the chorioallantoic membrance(CAM) of the immune deficient fertilized chicken eggs and the histopathologic changes of the CAM and gross morphologic changes of the implanted cancer tissues on CAM ere studied. The chemosensitivity tests using chicken CAM were performed for the 4 human bladder cancer tissues to mitomycin C, thiotepa and adriamycin. With this study, the following results were obtained: 1. The observation of the blood vessel on the chorioallantoic membrane was possible from the post-incubation 6th day group, but for the implantation of the cancer tissues, the blood vessels from the post-incubation 8th day group was appropriate. 2. The budding oif the host capillary vessel to the implanted cancer tissue were observed from the post-implantation second day. 3. The size of the post-implantation 7th day cancer tissues were varied from 2.3 to 9.2 folds to the size of the implantation day. 4. The total failure rate in experiment within post-operative 3rd day were 71.3 percent and the total failure rates in group who had the damage on the chorioallantoic membrance during operation was 82.5 percent. The failure rate of the experiment was declined acutely after post-operative 4th day. 5. The salvage of the eggs could be maintained until post-operative 7th day in 28.1 percent among chemosensitivity test group. 6. The 4 bladder cencer tissues which had the chemosensitivity test showed 1.6 to 7.1 fold growth to the inital implanted size and this meant resistance to the test drugs and these results were corresponded with clinical course.

Endocrine Study on Menstrual Irregularities in Wilson's Disease

We have investigated endocrine functions of 2 patients with Wilson's disease who showed oligomenorrhea or amenorrhea, The serum basal levels of hypothalamic, pituitary, thyroid, adrenal cortical and ovarian hormones were determined. Then stimulation tests were performed with GnRH(50 microgram/m2), TRH(7 microgram/Kg) and insulin(0.l U/Kg) in one intravenous bolus, Levels of LH, FSH, prolactin, GH, TSH, total testosterone, l7 beta-estradiol, free T3, T4, DHEA-S and cortisol were measured by standard radioimmunoassays. The endocrine profiles which represent functions of hypothalamus, pituitary, thyroid and adrenal cortex was all proved to be normal. Serum estradiol and total testosterone levels were 59.0 microgram/ml ( normal ; 60-130 microgram/ml) and 2.9 ng / dl (normal ; 0.l5-1.1 ng/dl) in one case, and 20.5 microgram / ml and 0.69 ng / dl in the other respectiviely. Low estradial and high total testosterone levels seen in these cases suggested ovarian dysfuncton. Interference of ovarian follicular aromatase activity due to passible copper intoxication could explain these findings as the cause of the menstrual irregularity of patients with Wilson's disease.

The Study on the Ultrasonographic Urethrogram of the Urethral Stricture / 대한비뇨기과학회지

The study of the ultrasonographic urethrogram on the male urethral stricture in 9 patients were performed. We could get the excellent three dimensional figures, which were demonstrating the nature of the urethral strictures in compared to the retrograde urethrogram. The ultrasonographic urethrography was useful in the diagnosis of the anterior urethral stricture, especially, but the delineation of the posterior urethra was difficult.

Study on the Histopathological Changes of the Subrenal Capsular Implantation of the Human Urologic Cancers / 대한비뇨기과학회지

The selection of the chemotherapeutic agents for the treatment of the urologic malignancy was one of the difficult problem in urologic practice. After the development of the in vivo sensitivity test using subrenal capsular implantation of the cancer tissue, a lot of the application of this assay were performed in various field of the advanced malignancies. We examined the histopathological changes of the implanted urologic cancer tissues under the renal capsule of the mice. The specimens, implanted under the renal capsule, were 14 cases of the bladder cancer, 2 cases of the renal cell carcinoma and one case of the prostatic carcinoma. In experiment, we used 472 immunocompetent normal mice and divide them into two groups, non-immunosuppressed normal mice and immunosuppressed group with intravenous infusion of the cyclophosphamide 200mg/kg 24 hours prior to assay. As the control group, we used athymic nude mice for human urologic cancer and C3H/He strain for MBT-2 bladder cancer. The results we found were as follow ; 1. The growth of the implanted cancer tissues was noticed in 270 mice among 291 which were sacrificed until the 6th postoperative day and the take rate was 92.8%. 2. The growth of the implanted cancer tissues was continuous until the 6th postoperative day progressively but reduced thereafter in immunocompetent group. But in immunosuppressed group, it showed progressive growth of the implanted tissue until the 8th postoperative day. The growth of the control group was similar to the immunosuppressed group, until the 6th postoperative day. 3. Calculation of the proportion of the host cellular infiltration in total dimension of the grafted tissue was done and in immunocompetent group, the 4th postoperative day group was 27.3%, the 6th postoperative group was 89.4% and the 8th postoperative group was 100%. But in contrast in immunosuppressed group, at the 4th postoperative day group was less than 10%, the 6th postoperative day was 29.4% and at the 8th postoperative day group was 91.7%. With above histopathological study, we conclude that the most easy and reasonable subrenal capsular assay(SRCA) in the in vivo chemosensitivity test for the selection of the anticancer chemotherapeutic agent for the treatment of the malignancy is the test performed under the immunosuppressed state with cyclophosphamide, 24 hours prior to SRCA, and the results is the most proper at the examination at postoperative 6th day after implantation.

Percutaneous Balloon Dilatation of Ureteral Stricture / 대한비뇨기과학회지

Percutaneous nephrostomy has become a common procedure in the field of the urology and the operation through the nephrostomy tract is one of the challenging procedure for the treatment of the disease of the kidney and ureter. We introduce a case of our successful experience of the percutaneous balloon dilatation of the ureteral stricture which was caused by previous ureterolithotomy.

Two Cases of the Prostate Papillary Adenoma in Posterior Urethra / 대한비뇨기과학회지

Prostate papillary adenoma is very rare benign disease in posterior urethra and until recently, it was called under the various different names. There is no case which was reported in this country until now. We experienced two cases of prostate papillary adenoma in patients over 55 years old who had combined with lower urinary tract obstructive symptoms and we report these cases with the review of literatures.

Paget`s Disease of the Scrotum: A Case Report with Local Lymph Node Invasion / 대한비뇨기과학회지

Extramammary Pager`s disease is a malignant condition. We experienced one case of Paget`s disease of scrotum in 76 years old male patient, The clinical presentation, treatment and prognosis of this lesion in the scrotum are discussed.

Pediatric Uroflowmetry / 대한비뇨기과학회지

The urinary flow rates of 917 children between 7 years and 15 years old were measures. The results were as follows . 1. Volume voided, average and maximum flow rate were higher according to increasement of age and sex. All values of female children were significantly higher than male children in same age and body Weight. 2. Voiding curves indicating the relationship between urinary flow and voided volume were obtained with logarithmic transformation. Voiding dates above 35kg were significantly higher than below 35kg and were similar to normal adults. 3. Fifth 10th, 15th, 20th and 25th percentiles nomograms were established with cumulative distribution.

Two Cases of Ectopic Ureteral Orifice / 대한비뇨기과학회지

We present a case of left ectopic ureteral orifice to the vagina with a hypoplastic kidney in a 15 year old girl and a case of ectopic ureteral orifice to the vaginal vestibule associated with bilateral complete double ureter in a 5 year old girl. They presented with urinary incontinence while normally secured voluntary voiding. Fifteen year old girl was treated with left nephrectomy and the other girl with heminephrectomy.

Two Experiences of Operation about Urogenital Anomalies Associated with Congenital Imperforate Anus / 대한비뇨기과학회지

The high incidence of genitourinary anomalies associated in patients with imperforate anus and rectum has long been recognized. The death of children suffering imperforate anus several years after satisfactory management of the alimentary lesion is often due fundamentally to oversight or poor management of a urologic lesion. We have recently two cases of imperforate anus associated with urogenital anomalies, urethrorectal and rectovaginal fistula.

Two Experiences of Operation about Urogenital Anomalies Associated with Congenital Imperforate Anus / 대한비뇨기과학회지

The high incidence of genitourinary anomalies associated in patients with imperforate anus and rectum has long been recognized. The death of children suffering imperforate anus several years after satisfactory management of the alimentary lesion is often due fundamentally to oversight or poor management of a urologic lesion. We have recently two cases of imperforate anus associated with urogenital anomalies, urethrorectal and rectovaginal fistula.

A Case of Emphysematous Pyelonephritis / 대한비뇨기과학회지

Emphysematous pyelonephritis is a rare complication of urinary tract infection and can occur in patients with diabetes mellitus or urinary obstruction. We recently treated a 52-year-old male patient with E. coli urinary tract infection and septicemia whose abdominal roentgenogram demonstrated a striking right pneumonephrogram as well as perirenal gas. Right nephrectomy was carried out to survive septic crisis. Timely surgical intervention after unsuccessful antibiotics and conventional medical measurement is life saving.

Non-transitional Cell Bladder Tumors / 대한비뇨기과학회지

Although it has been estimated that from 90 to 95% of all vesical neoplasms are of epithelial origin, and about 80% or more of carcinomas of the bladder are of transitional cell type, pratically all of the other constituents of the bladder have been known to give rise to benign and malignant tumors. A clinical observation was made on the non-transitional cell bladder tumors of the patients in the department of urology, Seoul National University Hospital during the period from 1966 to April, 1976. The following results were obtained: 1) During the period, 3699 patients were hospitalized, there were 293 cases of bladder tumors giving a rate of 7.9%. 2) Among 187 cases of bladder tumors there were 15 cases of non-transitional bladder tumors with a rate of 8%. 3) Age distribution was between 28 and 76 years. 4) Following symptoms could be found, hematuria in 93%, frequency 40%, dysuria 33% and other symptoms. 5) Squamous cell carcinoma was observed on 8 cases (4.3%), adenocarcinoma 3(1. 6%), metastatic carcinoma 2 (1.0%), malignant lymphoma 1 (0.5%). 6) Segmental resection was performed in 5 cases, total cystectomy 4, TUC 2 cases. Radiation and chemotherapy were combined in special cases. 7) 3 patients with squamous cell carcinoma died within 1 year after treatment.

Clinical Observation on the Penis Carcinoma / 대한비뇨기과학회지

Clinical observation was made on the 16 patients of penile carcinoma admitted to the Department of Urology, Seoul National University Hospital during the period from September, 1967 to August, 1976 and the following results were obtained. 1. The incidence of penile carcinoma was 0.5% of total inpatients of urologic department and 3.5% of male genitourinary tumors. 2. Age distribution was between 29 and 78, snowing highest incidence at 50-59 years. 3. Clinical findings were; mass 77%, discharge 28%, ulcer 25%, bleeding 13%, and inguinal lymphadenopathy 50%. 4. The average duration of the symptoms on admission to hospital was 10 months with the highest incidence in 1 to 6 months. 5. The locations of the tumors were; preputial cavity 87%, confined to glans 6%, penile shaft involved 6%. 6. Treatments were made with partial amputation in 50%, partial amputation with inguinal lymphadenectomy in 37%, and biopsy in 13%.

Studies on Male Infertility(VII): Clinical Observation on Klinefelter's Syndrome / 대한비뇨기과학회지

Klinefelter's syndrome was described in 1942 by Klinefelter, Reifenstein, and Albright and is characterized classically by small testes, azoospermia, gynecomastia, and elevated gonadotropins. The features become apparent during puberty. The cause of this syndrome is a developmental defect of the gonad resulting from a sex chromosome abnormality. Clinical observation was made on 8 patients with Klinefelter's syndrome in the Department of Urology, Seoul National University as follows; 1) The are was distributed from 19 years to 29 years. 2) The testes were small in size. Gynecomastia was noticed in 4 cases. Body hairs, beard and axillary hairs were rudimentary. The pubic hairs were absent, scanty or female type. The prostates were rudimentary in all cases. 3) chromosome study revealed 47, XXY in 6 cases and 46, XX in 2 cases. 4) The semen samples were devoid of spermatozoa. 5) The urinary gonadotropins for 24 hours elevated in 6 cases. The urinary 17-KS levels were between 6mg/day and 15.6mg/day. 6) Histologically there were atrophy and hyalinization with fibrosis of the seminiferous tubules. Increased number of Leydig cells in clumps were noticed adjacent to seminiferous tubules. 7) Treatment was hormonal therapy with testosterone.

Two Cases of Foreign Bodies in the Bladder / 대한비뇨기과학회지

We discovered two plastic tubes which were used as masturbating tools in the bladder. The following is a report of two young boys who slipped plastic tubes into the bladder through the urethra for the purpose of masturbation and lost them in the bladder while attempting to remove them. Case 1. : Y. D. S., 18 years-old, Admitted because of hematuria for 5 days. Cystoscopically, the bladder showed diffuse hyperemia and a coiled calcified plastic tube. It was removed by operation. The length of the tube was 0.58m and the diameter was O.4 cm. Case 2. : K. S. K., 18 years-old. Admitted because of urinary incontinence for 4 months. Cystoscopically. the bladder showed diffuse hyperemia and a coiled calcified plastic tube. It was removed by surgical operation. The length of the tube was 1.2m and the diameter was 0.5cm.