Vitamin C prevents radiation-induced endothelium-dependent vasomotor dysfunction and de-endothelialization by inhibiting oxidative damage in the rat

1. The present study was undertaken to determine whether endothelial function or morphology was altered in aortic rings of rats after irradiation, to investigate the mechanism of radiation effects on the endothelium and to examine the effect of vitamin C treatment against radiation-induced damage of the endothelium. 2. Female Sprague-Dawley rats were randomized into four groups (control, radiation, radiation + vitamin C, radiation + vitamin C + NG-nitro-L-arginine methyl ester (L-NAME); n = 10 for each group and n = 7 for the control group) and were irradiated with 10 Gy of 137Cs as a radiation source. Segments of the thoracic aorta were obtained and isometric tension, levels of 8-hydroxydeoxyguanosine (OH-dG) and immunohistochemical staining were measured. 3. Irradiation significantly impaired the acetylcholine-induced vasodilation of aortic segments, an effect that could be prevented by pretreatment with vitamin C (500 mg/kg per day). This beneficial effect of vitamin C was abolished by the addition of L-NAME (100 microg/kg per day), an inhibitor of nitric oxide (NO) synthesis. Irradiation significantly increased the level of OH-dG in the aorta (1.02 +/- 0.27 vs 2.61 +/- 0.78 OH-dG/105 deoxyguanosine (dG) for control and irradiated tissues, respectively; P < 0.01), an increase that was prevented by vitamin C treatment (1.59 +/- 0.23 OH-dG/105 dG; P < 0.01). Irradiation caused significant de-endothelialization (von Willebrand factor (vWF) staining was 93 +/- 7 vs 100% in irradiated and control tissues, respectively; P < 0.05) and this was prevented by vitamin C treatment (vWF staining 98 +/- 3%; P < 0.05). 4. Radiation caused endothelial damage and impaired NO production through oxidative injury, resulting in a selective impairment of endothelial-dependent vasodilation that could be prevented by vitamin C, partly through anti-oxidant mechanisms.     

Effect of sodium chloride on the gelation temperature, gel strength and bioadhesive force of poloxamer gels containing diclofenac sodium

Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository system containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. The mixtures of P 407 (15%) and P 188 (15-20%) existed as a liquid at room temperature, but gelled at physiological temperature. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. Furthermore, the poloxamer gels with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum of rabbits without difficulty and leakage, and retained in the rectum of rats for at least 6 h. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable and convenient rectal dosage form for diclofenac sodium.     

Liddle's syndrome: a report in a middle-aged woman

A 54-year-old woman with diabetes mellitus was hospitalized with generalized edema and weakness. She was also found to have hypertension, hypokalemia and metabolic alkalosis. Detailed examination showed subnormal plasma renin activity and plasma aldosterone concentration. Adrenal CT scanning revealed no adrenal tumor. A successful treatment with amiloride established the diagnosis of Liddle's syndrome for the patient. Liddle's syndrome, a rare hereditary disease usually found in young patients, should be considered in the differential diagnosis of hypertension even in elderly individuals.     

Serum ferritin in healthy subjects and type 2 diabetic patients

In order to study the relationship between the serum ferritin level and the components of the insulin resistance syndrome in type 2 diabetic patients, we evaluated fifty type 2 diabetic patients who were selected according to NDDG/WHO criteria from those patients attending Korea University Hospital from 1997 to 1998. Twenty-five healthy non-diabetic subjects of comparable age and sex distribution acted as a control group. The results showed that the value of log ferritin was higher in the type 2 diabetes patients than the control subjects, but not at a statistically significant level (p = 0.09). Log ferritin was correlated with fasting blood sugar level (r = 0.235, p = 0.048) and body mass index (BMI) (r = 0.285, p = 0.05). In the type 2 diabetic patients, log ferritin was correlated with fasting C-peptide (r = 0.478, p = 0.009). In the control subjects, log ferritin was correlated only with BMI (r = 0.477, p = 0.012). In a stepwise multiple regression analysis, the diabetic group showed a significant correlation between fasting C-peptide and log ferritin (p = 0.001). In the control group, the fasting sugar level was significantly correlated with log ferritin (p = 0.034). These results suggest that serum ferritin can be employed as a marker of not only glucose homeostasis but also insulin resistance both in type 2 diabetic and control subjects.     

Inter-relationships between arteriosclerotic risk factors: a meta-analysis

This study was performed to clarify the overall inter-relationships between the arteriosclerotic risk factors, including smoking, alcoholic consumption, obesity, serum cholesterol and triglyceride levels, high density lipoprotein, and systolic and diastolic blood pressure using a meta analysis method. The subjects of this study were included in 24 primary studies reported in Korea since 1980, which concerned arteriosclerotic risk factors. The results show that smoking is significantly associated with total cholesterol (R = .04), triglyceride (R = .10) and HDL-cholesterol (R = -.06). Alcohol consumption is also significantly and positively associated with all three serum lipid parameters: cholesterol (R = .04), triglyceride (R = .08) and HDL-cholesterol (R = .10). The effect of smoking and alcohol consumption on cholesterol levels were found to be almost equal. However, smoking has a predominant effect on triglyceride, whereas, alcohol consumption exerts an influence primarily on the HDL-cholesterol level. Obesity was positively correlated with cholesterol (R = .25) and triglyceride (R = .21), however, it was negatively correlated with HDL-cholesterol (R = -.14). It appears that the serum lipid parameter, which shows strongest correlation with obesity, is the total cholesterol level. Obesity also showed a significant correlation with systolic (R = .19) and diastolic blood pressure (R = .13). Blood pressure was also positively correlated with cholesterol (R = .18) and triglyceride (R = .26), however, it correlated negatively with HDL-cholesterol (R = -.23). In conclusion, the overall inter-relationships between the arteriosclerotic risk factors; smoking, alcohol consumption, obesity, serum lipid level and blood pressure were all found to be significant.     

Late presentation of ureteral injury after laparoscopic surgery

OBJECTIVE: To describe clinical presentation, etiology, and treatment of ureteral injuries recognized late in women who had gynecologic laparoscopies. METHODS: We reviewed the charts of 12 women who had delayed recognition of ureteral injuries between January 1991 and December 1998. RESULTS: Patients presented with fever, hematuria, flank pain, or peritonitis between 3 and 33 days postoperatively. The mechanism of ureteral injuries was electrocoagulation in seven women, laser ablation in one, and stapler ligation in four. The sites of injury were near the inferior margin of the sacroiliac joint on excretory urogram in eight women and near the ureterovesical junction in four. Three women initially treated with internal ureteral stents were subsequently treated with ureteroneocystostomy because of progression of urinary ascites in two and a delayed ureteral stricture in one. In nine patients, attempts at ureteral stenting were unsuccessful and immediate ureteral reconstruction was done. Outcomes were good in all cases. CONCLUSION: Delayed recognition of ureteral injury after gynecologic laparoscopy was associated with serious complications, and initial treatment with ureteral stenting was not useful. We advocate early open repair for those injuries.     

Adult T cell leukemia/lymphoma with lymphopenia in a Korean

We experienced a case of adult T cell leukemia/lymphoma (ATLL) in a 48-year-old Korean female, who has never been abroad since birth and no history of blood transfusion. The patient had hypercalcemia and multiple lymphadenopathy. Histopathologic study of left cervical lymph node (LN) and bone marrow (BM) revealed that infiltrates of malignant lymphoid cells were composed of small, medium and large cells with pleomorphic nuclei. Smears of peripheral blood (PB) showed lymphopenia (16%) with the appearance of a few atypical lymphoid cells (less than 2%), but not the typical clover leaf cells seen in ATLL. Immunophenotypic study of LN and BM revealed T cell phenotype. PB showed increased CD4+ T cell (T(H), CD3/CD4+, 57%) and decreased CD8+ T cell counts (T(S), CD3/CD8+, 6.7%). The sera of the patient and her family were reactive for HTLV-I antibody. The specific sequences of pol, env, and tax of HTLV-I DNA were detected in the lymphoma cells and peripheral blood mononuclear cells (PBMC) using polymerase chain reaction. Ultrastructural examination of PBMC confirmed numerous type c virus particles in extracellular space. This case was an acute type of ATLL without overt leukemic features in PB. Despite chemotherapy and intensive conservative treatment, she died 3 months after admission.     

Detection of human herpesvirus 8 DNA in pemphigus and chronic blistering skin diseases

Increased incidences of Kaposi's sarcoma and lymphoid malignancies have been observed in patients with pemphigus, and the human herpesvirus 8 (HHV-8) is very strongly associated with these tumors. Because the virus may be one of the triggering factors of pemphigus, we undertook this study to screen for the presence of HHV-8 in chronic blistering skin diseases including pemphigus. A total of 45 paraffin-embedded specimens were studied using nested polymerase chain reaction (PCR) with primers to amplify a 160-base pair HHV-8 fragment. HHV-8 DNA could be detected in 7 of 9 patients with pemphigus vulagris, and 1 of 2 with pemphigus foliaceus. All specimens of other blistering skin diseases were negative for HHV-8. On sequencing PCR products, the sequences were almost identical with the prototypic sequence for HHV-8, and a few base- pair substitutions at 1086C-T and 1139A-C were detected. The results of our study suggests that HHV-8 might have trophism for pemphigus lesions. Further studies including comparison of HHV-8 DNA load in both lesional and normal skin in the same patient, serological and animal studies would be helpful to study the relationship between HHV-8 and pemphigus.