Radiation-induced apoptosis in peritoneal resident macrophages of C3H mice

Gamma ray-radiation induced significant apoptosis in peritoneal resident macrophages (PRMs) of C3H/HeJ (C3H) mice, but not in other strains of mice. To investigate the role of DNA damage in the apoptosis, DNA damage was quantified in PRMs by use of the alkaline single-cell gel electrophoresis (Comet) assay. No significant difference was found between C3H and C57Black/6 mice in either radiation-induced DNA damage or repair. Radiation induced apoptosis at the same levels in PRMs of p53 knockout mice and atm knockout mice as those of wild-type C3H mice; however radiation-induced apoptosis was significantly less extensive in the thymocytes of these mutant mice than in those of wild-type mice. Apoptosis was also induced at the same level by an irradiation in PRMs of C3H scid mice as in those of wild-type C3H mice. Therefore it was suggested that radiation-induced DNA damage and TP53, ATM, or DNA-PK-mediated cellular responses occurring downstream thereof were not involved in the radiation-induced apoptotic cell death in C3H mouse PRMs.     

Thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in hepatocellular carcinoma and metastatic liver cancer

Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are considered to be key enzymes affecting the prognosis for patients with various cancers. We tried to prove the correlation of TP and DPD expression in hepatocellular carcinoma (HCC) and liver metastasis. We quantified TP and DPD levels by an enzyme-linked immunosorbent assay (ELISA) in the tumor (T) and adjacent normal tissue (N) obtained from 8 HCC patients, and 11 liver metastasis patients together with 9 of their primary cancers. TP levels were higher in the primary cancer, liver metastasis, and HCC compared with each adjacent tissue. TP levels were higher in HCC than in liver metastasis, and TP levels in the adjacent tissues of HCC were also higher than those in adjacent tissues of liver metastasis. TP levels were higher in liver metastasis than in primary cancer, and TP levels in adjacent tissues of liver metastasis were also higher than those in adjacent tissues of primary cancer. However, there were no differences in TP T/N ratio between HCC and liver metastasis, and between primary cancer and liver metastasis. DPD levels were lower in the liver metastasis compared with the adjacent liver tissues, and DPD levels in liver metastasis or its adjacent liver tissues were higher than those in primary cancer or its adjacent tissues. There were no differences in DPD T/N ratio between HCC and liver metastasis, and between primary cancer and liver metastasis. Thus, we demonstrated that TP was highly expressed in liver malignancy. We may be able to increase the success of anticancer chemotherapy for liver malignancy while decreasing the side effects by analysis of T/N ratios in TP, DPD, and TP/DPD in addition to TP expression.     

Evaluation of psychological factors in orthodontic patients with TMD as applied to the "TMJ Scale"

Physical and psychological evaluation have been required for TMD patients whose problems are multi dimensional. The questionnaire named the "TMJ Scale" was created to differentiate subjective TMD symptoms of patients. The purpose of this study was to clarify the reliability of the TMJ Scale for Japanese orthodontic patients with TMD and to differentiate the symptoms. Fifty orthodontic patients (average age 21y4m) with a chief complaint of TMD symptoms were compared with thirty patients (average age 21y1m) without TMD symptoms. The results were as follows: female patients in the symptom group in particular showed a higher degree of stress due to the chronic pain and abnormalities than those in the non-symptom group. Significant differences were observed in Pain Report, Joint Dysfunction and Global Scale at the 0.1% significant level, in Non-TM Disorder, Psychological Factor and Chronicity at the 1% level, and in Palpation Pain and Perceived Malocclusion at the 5% level in females. Few psychological problems were observed in male patients in the symptom group. Significant differences were observed in Range of Motion limitation at the 5% level in males. The differences in the psychological factors between male and female patients were clarified by using the TMJ Scale. These findings suggested that it was useful to differentiate the multiple symptoms, especially the psychological factors, by using the TMJ Scale for orthodontic patients with TMD.     

Development of a new extracorporeal whole-liver perfusion system

We have developed a new extracorporeal whole-liver accommodation device in which a whole swine liver is placed in a physiological state by modeling the intraabdominal arrangement in the pig body, with the liver supported by a special inferior vena cava tube. Furthermore, we employed a diaphragm-type artificial heart in our system to produce pulsatile blood flow through the hepatic artery, which is considered to be indispensable to dilate peripheral vessels and supply oxygenated whole blood to the peripheral liver tissue. Beneficial effects were demonstrated in visual findings and bile juice secretion. The color of the liver surface in our system remained bright red, indicating that the liver vessels were well drained and free from congestion, and bile juice secretion was maintained at more than 10ml/h throughout the perfusion period. Our system exhibited excellent ammonia removal and urea nitrogen synthesis, and serum aspartate aminotransferase levels showed no increase, indicating the absence of hepatocyte destruction. Histological findings showed that the liver could expand appropriately and was free from compression caused by its own weight. In conclusion, our original liver accommodation device enabled appropriate expansion of the whole liver and supplied adequate oxygenated blood to peripheral areas by means of a pulsatile pump.     

Mild hypercapnia induces vasodilation via adenosine triphosphate-sensitive K+ channels in parenchymal microvessels of the rat cerebral cortex

BACKGROUND: Carbon dioxide is an important vasodilator of cerebral blood vessels. Cerebral vasodilation mediated by adenosine triphosphate (ATP)-sensitive K+ channels has not been demonstrated in precapillary microvessel levels. Therefore, the current study was designed to examine whether ATP-sensitive K+ channels play a role in vasodilation induced by mild hypercapnia in precapillary arterioles of the rat cerebral cortex. METHODS: Brain slices from rat cerebral cortex were prepared and superfused with artificial cerebrospinal fluid, including normal (Pco2 = 40 mmHg; pH = 7.4), hypercapnic (Pco2 = 50 mmHg; pH = 7.3), and hypercapnic normal pH (Pco2 = 50 mmHg; pH = 7.4) solutions. The ID of a cerebral parenchymal arteriole (5-9.5 microm) was monitored using computerized videomicroscopy. RESULTS: During contraction to prostaglandin F2alpha (5 x 10(-7) m), hypercapnia, but not hypercapnia under normal pH, induced marked vasodilation, which was completely abolished by the selective ATP-sensitive K+ channel antagonist glibenclamide (5 x 10(-6) m). However, the selective Ca2+-dependent K+ channel antagonist iberiotoxin (10(-7) m) as well as the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (10(-4) m) did not alter vasodilation. A selective ATP-sensitive K+ channel opener, levcromakalim (3 x 10(-8) to 3 x 10(-7) m), induced vasodilation, whereas this vasodilation was abolished by glibenclamide. CONCLUSION: These results suggest that in parenchymal microvessels of the rat cerebral cortex, decreased pH corresponding with hypercapnia, but not hypercapnia itself, contributes to cerebral vasodilation produced by carbon dioxide and that ATP-sensitive K+ channels play a major role in vasodilator responses produced by mild hypercapnia.     

Multiple intracerebral microhemorrhages associated with primary aldosteronism: a case report

We have observed dot-like low intensity spots (a dot-like hemosiderin spot: dotHS) on T2*-weighted (T2*-w) MRI, subsequently diagnosed histologically as previous microbleeds associated with lipohyalinosis, amyloid angiopathy and cerebral small vessel disease (SVD) including an intracerebral hematoma (ICH) and a lacunar infarction. According to the literature, primary aldosteronism (PA), characterized by hypertension, is related to SVD. A 49-year-old female with a long history of untreated hypertension secondary to PA was admitted to our hospital for medical examinations on July 18th, 2000. She had the stepwise development of dementia, dysarthria and gait disturbance (right hemiparesis). CT and MRI demonstrated multiple lacunar infarctions. She was readmitted to our hospital on Jan 23rd, 2002. A neurological examination revealed right hemiparesis, dysarthria and consciousness disturbance. CT on admission demonstrated ICH in the left midbrain. Six days after the hemorrhage, T2*-w MRI showed thirty-two dotHSs in the basal ganglias and the cortical-subcortical regions. The incidence of ICH in patients with hypertension secondary to PA is reported to be higher than in patients with essential hypertension. Multiple dotHS may be associated with ICH, lacunar infarction, and severe microangiopathy related to hypertension secondary to PA.     

Laterality of the performance of glaucoma mass screening using frequency-doubling technology

PURPOSE: This study investigated laterality during the performance of glaucoma mass screening with a frequency-doubling technology perimetry test. MATERIALS AND METHODS: A frequency-doubling technology screening mode (C-20-1, version 2.6) test was performed on both eyes of 14,784 persons. Subjects with visual field abnormalities detected by the frequency-doubling technology test or with fixation error underwent retesting without a specified interval for rest. Consequently, 206 subjects who fulfilled the screening criteria of the frequency-doubling technology-based glaucoma screening protocol [FDT-GSP(+)] were further investigated using the Humphrey visual field analyzer (30-2). As a result, 74 right eyes and 57 left eyes were shown to have definite glaucoma. RESULTS: Frequency-doubling technology data for the left eye demonstrated a significantly (P<0.001) higher rate of artifacts, such as no reproducibility of results between the first and second tests (left/right: 2.4%/1.7%) as well as fixation errors (left/right: 2.8%/1.0%). The false-positive rate of the FDT-GSP for glaucoma was more than 1.5-fold higher in the left eye than in the right eye (16.3%/9.8%). In the case that either eye exhibited FDT-GSP(+), the positive predictive value of the FDT-GSP for definite glaucoma in the left eye was almost half of that in the right eye (28.4% vs. 53.8%). Specificity of the FDT-GSP for detection of definite glaucoma also exhibited a lower trend (P = 0.097) in the left eye (44.6%) than in the right eye (55.3%), but the sensitivity of the test was similar in both eyes (91.2% vs. 90.5%, respectively). CONCLUSIONS: When frequency-doubling technology-based mass screening is performed on the general population, performance is lower for the left eye than for the right eye. This performance disparity is likely to be primarily associated with a difference in specificity.     

Therapeutic usefulness of Keishi-bukuryo-gan for diabetic nephropathy

Keishi-bukuryo-gan is a traditional herbal medicine, which is used clinically as a vascular system disorder-eliminating drug. In this study, its effect on the progression of diabetic nephropathy in experimental rats was investigated. The diabetic nephropathy model used in this study shows functional and morphological changes of the kidney resembling those seen in patients with diabetic nephropathy. Increased proteinuria and serum urea nitrogen and creatinine levels and decreased creatinine clearance, which are important parameters of renal function, were observed in rats with diabetic nephropathy. Pathological examination of the kidney revealed diffuse, nodular and exudative lesions and arteriolar hyalinosis. The deterioration of renal function was ameliorated in rats treated with Keishi-bukuryo-gan for 15 weeks and these results agreed with the renal histological findings. In addition, metabolic abnormalities mediated by persistent hyperglycaemia (the glycation reaction, excessive polyol pathway activity, oxidative stress and lipid metabolic abnormalities) were also observed. However, Keishi-bukuryo-gan reduced accumulation of advanced glycation end products, determined by measuring fluorescence, and serum lipid peroxidation, triglyceride and total cholesterol levels dose-dependently. Thus, this study indicates the potential therapeutic usefulness of Keishi-bukuryo-gan for retarding the progression of renal damage and suggests that its beneficial effects were due to its ability to improve metabolic abnormalities associated with diabetes.     

Clinical evaluation of the effect of daio (rhei rhizoma) on the progression of diabetic nephropathy with overt proteinuria

We studied the effect of traditional herbal medicines containing daio (Rhei Rhizoma) on the long-term progression of diabetic nephropathy with overt proteinuria in eight patients [mean age 60 (45-73) years; duration of diabetes 18 (7-36) years]. At the beginning of the study, mean HbA1c was 8.2% and mean serum creatinine was 1.0 +/- 0.3 mg/dl. Everypatient had diabetic neuropathy and retinopathy. Three of the patients had hypertension and four had ischemic heart disease. After 107 +/- 25 months, the mean serum creatinine level had significantly increased to 4.8 +/- 2.6 mg/dl. The mean serum creatinine levels of five patients not advancing to dialysis treatment increased from 1.2 +/- 0.3 to 3.2 +/- 1.0 mg/dl, and the three patients requiring dialysis increased from 0.8 +/- 0.1 to 7.5 +/- 2.1 mg/dl. In the control group, treated without traditional herbal medicines, the mean serum creatinine level had significantly increased from 1.0 +/- 0.3 to 9.5 +/- 1.9 mg/dl after 71 +/- 12 months. All of the control group required dialysis treatment. Diabetic nephropathy with overt proteinuria is reported to develop into renal failure after 6-7 years. In this retrospective study, traditional herbal medicines with Daio were considered to be effective in prolonging the pre-dialysis period of diabetic nephropathy.