SAR analysis of the improved resonant cavity applicator with electrical shield and water bolus for deep tumors by a 3-D FEM.

This paper discusses the improvements of the re-entrant resonant cavity applicator, such as an electromagnetic shield and a water bolus for concentrating heating energy on deep tumors in an abdominal region of the human body. From our previous study, it was found that the proposed heating system using the resonant cavity applicator, was effective for heating brain tumors and also for heating other small objects. However, when heating the abdomen with the developed applicator, undesirable areas such as the neck, arm, hip and breast were heated. Therefore, we have improved the resonant cavity applicator to overcome these problems. First, a cylindrical shield made of an aluminum alloy was installed inside the cavity. It was designed to protect non-tumorous areas from concentrated electromagnetic fields. Second, in order to concentrate heating energy on deep tumors inside the human body, a water bolus was installed around the body. Third, the length of the lower inner electrode was changed to control the heating area. In this study, to evaluate the effectiveness of the proposed methods, specific absorption rate (SAR) distributions were calculated by FEM with the 3-D anatomical human body model reconstructed from MRI images. From these results, it was confirmed that the improved heating system was effective to non-invasively heat abdominal deep tumors.

Heating properties of a new hyperthermia system for deep tumors without contact.

In this paper, heating properties of the proposed hyperthermia system for non-invasive treatment of deep tumors are discussed. Our heating system is composed of a large size resonant cavity applicator. In this heating method, a human body is placed between the two inner electrodes. It is heated by electromagnetic fields stimulated in the cavity without contact between the surface of the human body and the applicator. First, we presented the experimental results of heating a cylindrical agar phantom and a cylindrical fat-agar phantom using the proposed system. From the thermal images of the heated phantoms, the center of the agar was locally heated to maximum temperature. Second, we presented the experimental results of heating a mini pig. In the heating experiment, temperature measurements were performed by using fiber-optical thermometers inserted in four locations inside the mini pig. From the results, the deepest region of the liver was heated to the highest temperature 43.3 °C.

A new heating method with dielectric bolus using resonant cavity applicator for brain tumors.

In this paper, we discuss a new method of controlling heating location in the proposed resonant cavity applicator. A dielectric bolus was used to non-invasively treat brain tumors. We have already confirmed that our heating system using resonant cavity is useful to non-invasively heat brain tumors. In order to heat tumors occurring at various locations, it is necessary to control the heating area with our heating system. First, we presented the proposed heating method and a phantom model to calculate temperature distributions. The results of temperature distributions were discussed. Second, a 3-D human head model constructed from 2-D MRI images was presented. The results of specific absorption rate distributions were discussed. From these results, it was found that the proposed heating method was useful to non-invasively treat brain tumors.

Heating properties of coaxial needle applicator made of SMA for hyperthermia treatments.

This paper describes heating properties of the developed coaxial needle applicator made of a shape memory alloy (SMA) for brain tumor hyperthermia treatments to avoid undesirable hotspots. We estimated the temperature distribution inside an agar phantom by the finite element method (FEM) and heated the agar phantom with the developed needle applicator.

SAR analysis of a re-entrant resonant cavity applicator for brain tumor hyperthermia treatment with a 3-D anatomical human head model.

A re-entrant resonant cavity applicator system for non-invasive brain tumor hyperthermia treatments was presented. We have already confirmed the effectiveness of the heating properties of this heating system with cylindrical agar phantoms and with computer simulations.

Heating properties of the needle type applicator made of shape memory alloy by 3-D anatomical human head model.

Since the human brain is protected by the skull, it is not easy to non-invasively heat deep brain tumors with electromagnetic energy for hyperthermia treatments. Generally, needle type applicators were used in clinical practice to heat brain tumors. To expand the heating area of needle type applicators, we have developed a new type of needle made of a shape memory alloy (SMA). In this paper, heating properties of the proposed SMA needle type applicator were discussed. Here, in order to apply the SMA needle type applicator clinically. First, we constructed an anatomical 3-D FEM model from MRI and X-ray CT images using 3D-CAD software. Second, we estimated electric and temperature distributions to confirm the SMA needle type applicator using the FEM soft were JMAG-Studio. From these results, it was confirmed that the proposed method can expand the heating area and control the heating of various sizes of brain tumors.

Heating properties of non-invasive hyperthermia treatment for abdominal deep tumors by 3-D FEM.

This paper discusses the heating properties of a new type of hyperthermia system composed of a re-entrant type resonant cavity applicator for deep tumors of the abdominal region. In this method, a human body is placed in the gap of two inner electrodes and is non-invasively heated with electromagnetic fields stimulated in the cavity. Here, we calculated temperature distributions of a simple human abdominal phantom model that we constructed to examine the heating properties of the developed hyperthermia system. First, the proposed heating method and a simple abdominal model to calculate the temperature distribution are presented. Second, the computer simulation results of temperature distribution by 3-D FEM are presented. From these results, it was found that the proposed simple human abdominal phantom model composed of muscle, fat and lung was useful to test the heating properties of our heating method. Our heating method was also effective to non-invasively heat abdominal deep tumors.

Finite element analysis of the needle type applicator made of shape memory alloy.

In this paper, we propose a new heating method in which we use shape memory alloy (SMA) in a needle type applicator for brain tumor hyperthermia. In order to expand the heating area of a needle type applicator and to control the heating pattern for various sizes of tumors, some kinds of SMA needle type applicators were developed. To apply the proposed heating method safely to clinical hyperthermia, it is necessary to make appropriate thermal distribution to the region of the brain tumor. However, it is not easy to predict the three dimensional temperature distribution during the human brain tumor hyperthermia. Therefore, we estimated the temperature distribution inside the agar phantom by the finite element method (FEM). Here, first, the computer simulation results of temperature distributions under the different heating times are discussed. Second, a comparison of the heating properties obtained by using the needle type electrodes made of different shaped SMA is discussed. From these results, it is confirmed that the proposed heating method can expand the heating area and control the heating pattern for the various sizes of brain tumors.

Induction of apoptosis in HL-60 cells treated with medicinal herbs.

In order to develop a new apoptosis inducer, we screened 22 crude drugs for their apoptosis-inducing activity. It was found that Glycyrrhiza uralensis, Cynomorium songaricum, Eucommia ulmoides, Phellodendron amurense, Cinnamomum cassia and Paeonia lactiflora induced the death of HL-60 cells. To investigate the mechanism of apoptosis induced by these six crude drugs, the mitochondrial transmembrane potential and the activity of caspase-3 were measured. Reduced mitochondrial transmembrane potentials within 12 hours after the administration of Glycyrrhiza uralensis, Cynomorium songaricum, Phellodendron amurense and Paeonia lactiflora, and within 24 hours after the administration of Eucommia ulmoides and Cinnamomum cassia were observed. All of the six apoptosis-inducing crude drugs increased caspase-3 activity within 12-36 hours after administration. After further examining the apoptosis-inducing activity of berberine, palmatine, panelofuroline and glycyrrhizin, which were the ingredients obtained from Phellodendron amurense, Glycyrrhiza uralensis and Paeonia lactiflora, it was found that only berberine could induce apoptosis. From these results, it was concluded that the apoptosis induced by the six crude drugs (Glycyrrhiza uralensis, Cynomorium songaricum, Eucommia ulmoides, Phellodendron amurense, Cinnamomum cassia and Paeonia lactiflora) occurred via the mitochondrial route and that the apoptosis-conducting mechanism acted through a cascade involving caspase-3.

Articular cartilage degradation and de-differentiation of chondrocytes by the systemic administration of retinyl acetate-ectopic production of osteoblast stimulating factor-1 by chondrocytes in mice.

OBJECTIVE: Vitamin A derivatives are widely used therapeutic agents for the treatment of dermatological and rheumatological disorders. Long-standing administration of these drugs, in turn, causes skeletal changes including ossification of ligaments, premature fusion of epiphyses and abnormalities of modeling. Recent in vitro experiments have further suggested that retinoid treatment of cultured chondrocytes may cause apoptotic cell death. The present study aims to address detailed cartilage changes associated with in vivo administration of vitamin A derivatives. METHODS: Retinyl acetate was administrated to experimental mice, C3H-Heston, for more than 12 months. Modified morphometry on the articular cartilage and fluorescent labeling of the subchondral bone were carried out to address the changes in the articular cartilage and subchondral bone. In order to address the detailed chondrocytes phenotypes, electron microscopy was carried out. Since findings of these studies suggested that biological properties of the cartilage matrix might be altered, the present study also immunolocalized functional matrix molecules, type I collagen and osteoblast-stimulating factor-1 (OSF-1). RESULTS: Histomorphometry demonstrated that retinoid administration lead to progressive atrophy of the articular cartilage with concomitant proliferation of subchondral bone. Furthermore, detailed light and electron microscopy suggested that the subchondral bone proliferates into the degenerating cartilage. The affected articular cartilage also resembled that of osteoarthritis in terms of ectopic type I collagen production. Furthermore, the affected articular cartilage produced a developmentally regulated matrix molecule, osteoblast-stimulating factor-1 (OSF-1) that is normally expressed in both the fetal cartilage and the epiphyseal growth plate cartilage but not in the articular cartilage. CONCLUSION: The present results indicate that the systemic retinoid administration may alter the biological properties of the articular cartilage.

Antipruritic and antinociceptive effects of Chenopodium album L in mice.

The ethanolic extract from the fruits of Chenopodium album L. (FCAL), orally administered at doses of 100-400 mg/kg, dose-dependently inhibited scratching behavior induced by 5-HT (10 micro g per mouse, s.c.) or compound 48/80 (50 micro g per mouse, s.c.) in mice. But it failed to affect hind paw swelling induced by 5-HT or compound 48/80 in mice at doses of 100 and 200 mg/kg and only showed a relatively weak inhibition on the swelling at a higher dose of 400 mg/kg. In addition, FCAL (200 and 400 mg/kg) significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and the inflammatory pain response induced by an intraplantar injection of formalin in mice. At a dose of 400 mg/kg, it also inhibited the neurogenic pain response of formalin test. In conclusion, FCAL possesses antipruritic and antinociceptive activities and the antinociceptive effects are not secondary to anti-inflammatory effects. The findings support evidence for the clinical use of FCAL to treat cutaneous pruritus.

General pharmacological properties of Sho-seiryu-to (TJ-19) extracts.

The general pharmacological properties of TJ-19 extracts were orally investigated in various experimental animals. TJ-19 extracts showed no effect on general behavior and on central nervous system such as spontaneous locomotor activity, proconvulsant and anti-convulsant responses, analgesic activity, body temperature and hexobarbital sleeping time at all doses of 0.5, 1 and 2 g/kg in mice. Further, TJ-19 extracts showed no effect on contractile responses of isolated guinea pig ileum induced by acetylcholine, histamine and BaCl2 at concentrations of 10(-6), 10(-5), and 10(-4) g/ml. TJ-19 extracts, however, increased the respiratory rate, heart rate, blood pressure, systolic pressure, diastolic pressure, and decreased the blood flow in dogs at all doses of 0.5, 1 and 2 g/kg via duodenal administration. Further, TJ-19 extracts decreased the interval of PR and QT of EKG parameters in dogs at doses of 1 and 2 g/kg. TJ-19 extracts increased the intestinal transport of charcoal meal in rats at doses of 1 and 2 g/kg. TJ-19 increased the urinary Na+ excretion at all doses of 0.5, 1, and 2 g/kg, and increased the urinary K+ and Cl- excretion at 1 and 2 g/kg, although it showed no effect on urine volume output in rats. These data suggest that TJ-19 stimulates the sympathetic nervous system function at a pharmacological dose of under 0.5 g/kg, and has possibility to increase the intestinal peristalsis and urinary electrolyte excretion at higher doses.

Antidiabetic activity of the rhizoma of Anemarrhena asphodeloides and active components, mangiferin and its glucoside.

The antidiabetic activity of the rhizoma of Anemarrhena asphodeloides was investigated in KK-Ay mice, an animal model of genetic type 2 diabetes. The water extract of the rhizoma (AA) (90 mg/kg) reduced blood glucose levels from 570 +/- 29 to 401 +/- 59 mg/dl 7 h after oral administration (p<0.05) and also tended to reduce serum insulin levels in KK-Ay mice. AA-treated KK-Ay mice had significantly reduced blood glucose levels in an insulin tolerance test. Based on these results, the antidiabetic mechanism of AA may be due to decreased insulin resistance. In addition, the active components of AA were confirmed to be mangiferin and its glucoside.

Protective effects of Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) against atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits.

We investigated the protective effects of the traditional Japanese herbal medicine Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang in Chinese) (SRBT) against hypercholesterolemia and atherosclerotic lesions. We focused on atherosclerosis using female heterozygous Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. The total plasma cholesterol levels increased for up to 12 weeks after beginning a diet containing 0.1% cholesterol and then reached a plateau of about 600 mg dl(-1). When SRBT was administered at a dose of 1.0 g kg(-1)per day for 24 weeks, total plasma cholesterol levels were significantly decreased after 20-24 weeks. On the other hand, pravastatin at a dose of 10 mg kg(-1)per day produced a significant decrease in total plasma cholesterol levels from 4 to 24 weeks (about 105-130 mg dl(-1)). Moreover, 1.0 g kg(-1)per day of SRBT significantly decreased plasma low density lipoprotein (LDL) cholesterol levels but did not change either very low density lipoprotein (VLDL), or high density lipoprotein (HDL) cholesterol levels. Animals that received pravastatin had significantly decreased LDL cholesterol levels and VLDL cholesterol levels after 8 weeks and at 24 weeks. We also examined the expression of apoB, E and LDL receptor mRNA levels in the liver at 24 weeks after beginning the administration of 1.0 g kg(-1)per day of SRBT. Both apoE and LDL receptor mRNA levels were significantly increased compared with those in rabbits receiving the 0.1% cholesterol diet. SRBT at a dose of 1.0 g kg(-1)per day significantly depressed the intimal surface area of the thoracic aortae involved with atheromatous plaques. The present results suggest that SRBT may protect against hypercholesterolemia and atheromatous lesions by affecting apoE and LDL receptor mRNA gene expression in the liver.

Testosterone 5alpha-reductase inhibitory active constituents from Anemarrhenae Rhizoma.

The diethyl ether extract of Anemarrhenae Rhizoma (rhizomes of Anemarrhena asphodeloides Bunge) showed testosterone 5alpha-reductase inhibitory activity. Two major constituents, cis-hinokiresinol (1) and 2,6,4'-trihydroxy-4-methoxybenzophenone (2) were identified as the active principles. The inhibitory activity of 1 was superior to that of ethinylestradiol, but that of 2 was weak.

Modulatory effect of aliphatic acid amides from Zanthoxylum piperitum on isolated gastrointestinal tract.

beta-Sanshool and gamma-sanshool, unsaturated aliphatic acid amides isolated from the pericarpium of Zanthoxylum piperitum De Candolle (Rutaceae), relax the circular muscle of the gastric body, as well as contract the longitudinal muscle of the ileum and distal colon in an experimental system using the gastrointestinal tract isolated from a guinea pig.

Antidiabetic activity of a xanthone compound, mangiferin.

Mangiferin (MF) isolated from Anemarrhena asphodeloides Bunge rhizome, was tested for antidiabetic activity in KK-Ay mice, an animal model of type-2 diabetes. MF lowered the blood glucose level of KK-Ay mice 3 weeks after oral administration (p < 0.01). However, no effect on the blood glucose level in normal mice was seen, indicating that MF could be useful in treating type-2 diabetes. In addition, MF improved hyperinsulinemia and, on insulin tolerance test, reduced blood glucose levels of KK-Ay mice. From these findings, it seems likely that MF exerts its antidiabetic activity by decreasing insulin resistance.

Anti-androgenic activity of Myricae Cortex--isolation of active constituents from bark of Myrica rubra.

The aqueous ethanol extract of Myricae Cortex (bark of Myrica rubra Sieb. et Zucc., Myricaceae) showed in vitro testosterone 5alpha-reductase inhibitory activity and in vivo anti-androgenic activity using growth of flank organ in castrated Syrian hamsters and/or hair regrowth after shaving in testosterone-treated C57Black/6CrSlc mice. Three constituents, myricanone, myricanol, and myricetin were identified as the main active principles.

Study on anti-Oketsu activity of rhubarb II. Anti-allergic effects of stilbene components from Rhei undulati Rhizoma (dried rhizome of Rheum undulatum cultivated in Korea).

Methanol extract (RM-ext) obtained from the dried rhizome of Rheum undulatum was screened for activity in experimental models of type I allergy. RM-ext exhibited the inhibition on 48-h homologous passive cutaneous anaphylaxis (PCA) in rats and an antigen-induced histamine release from rat peritoneal mast cells. Among nine stilbenes isolated from RM-ext, seven inhibited the histamine release. Rhapontigenin (compound 1), piceatannol (2) and piceatannol 3'-beta-D-glycoside (6) with oral administration showed the inhibition on PCA. Compounds 1 and 2 exhibited the inhibitory effect on sheep red blood cell-induced delayed-type hyper sensitivity (SRBC-DTH) of type IV allergic model. These results indicated that the rhizome of Rheum undulatum inhibits the allergic reactions and that these inhibitory effects may be partially attributable to the stilbenes mentioned above.

A natural history of adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) from preclinical to clinically overt Cushing's syndrome.

A 49-year-old man was referred to our hospital for the treatment of gallstones in 1993. Bilateral adrenal nodular masses were detected incidentally by abdominal computed tomography. He had no clinical signs of Cushing's syndrome such as central obesity, striae of skin and diabetes mellitus. We performed cholecystectomy and partial adrenalectomy of right adrenal gland as a biopsy, and diagnosed him as preclinical Cushing's syndrome due to adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) based on endocrinological and histological examinations. We followed him up for 7 years. During the observation period, the sizes of both adrenal glands increased gradually, and finally serum cortisol level increased beyond normal range, and he showed a Cushingoid appearance such as moon face and central obesity. His skin became atrophic and very fragile, and the bone mineral density of his lumbar spine was extremely low. Serum cortisol level was elevated, and plasma ACTH level was always suppressed. Urinary excretion of 17-hydroxycorticosteroid and free cortisol were increased. Diurnal rhythm of cortisol and ACTH was completely lost and high dose (8 mg/day) dexamethasone did not suppress urinary 17-hydroxycorticosteroid excretion. He became clinically overt Cushing's syndrome. We recommended total adrenalectomy, but he refused it. It is important to know the natural history of preclinical Cushing's syndrome due to AIMAH when choosing an adequate treatment.