Controlling interfered area in interferential current stimulation by electrode-area patterning.

Interferential current therapy is a noninvasive therapy using simultaneously two or more medium-frequency currents passing through tissue. By controlling the interfered area of the current flows, selective stimulation is possible in target muscles, including deep muscles. However, controlling the interfered area or the intensity of the current precisely is still lacking. Using simulations based on a biological model of the thigh as well as electrical muscle stimulation (EMS) experiments, we investigated the influence of electrode area ratio in changing the interfered area of the currents. Simulation and experiments were conducted under the same conditions, whereby current signals were applied through electrodes placed on the quadriceps and hamstring with an electrode area ratio of either 1:1 or 3:1. A comparison of the simulation results showed that the interferential current density decreased near the larger area electrode but increased near the smaller area electrode. In addition, the EMS experiment also showed that the quadriceps were stimulated using electrodes in a 1:1 area ratio, and the hamstrings were stimulated using electrodes in a 3:1 area ratio. These results demonstrated the possibility of controlling the area application of interferential current through electrode area patterning.

Carcinosarcoma of the fallopian tube with disappearance of carcinoma cells by neoadjuvant chemotherapy: case study.

The authors report a case of carcinosarcoma (CS) of the fimbria of the fallopian tube in which carcinoma cells disappeared with neoadjuvant chemotherapy (NAC). A 74-year-old woman visited the present hospital with a large pelvic mass and pleural effusion. A magnetic resonance image of the tumor was highly suggestive of ovarian carcinoma. Due to the presence of both serous.adenocarcinoma cells in pleural effusion and pulmonary thrombosis, the patient was given NAC consisting of carboplatin plus paclitaxel (TC) and anticoagulant therapy with warfarin potassium. With six courses of NAC, the pleural effusion and pulmonary thrombosis disappeared, and the tumor decreased 36.2% in greatest diameter. Maximum debulking surgery was then performed. The tumor was found to be located in the fimbria of the right fallopian tube. Hysterectomy and bilateral salpingo-oophorectomy were performed, and histologic examination revealed chondrosarcoma with the presence of necrotic epithelial cells. The necrotic areas were interspersed with papillary structures, and immunohistochemical study showed positivity for CK7 and negativity for CK20, p53, and estrogen receptor (ER), indicating serous adenocarcinoma. Thus, heterologous CS with disappearance of viable carcinoma cells by NAC was diagnosed. The patient was given adjuvant chemotherapy consisting of three courses of TC, and there has been no evidence of disease for 20 months. The authors' experience in this case of gynecologic CS indicates that a serous adenocarcinomatous component of tubal CS can be well cured by TC-based NAC.

Optic cup enlargement followed by reduced optic nerve head circulation after optic nerve stimulation.

PURPOSE: To investigate changes in optic nerve head (ONH) circulation, visual evoked potentials (VEPs), and ONH cupping after stimulation of the optic nerve. METHODS: Electrodes were fixed above the optic chiasma in rabbits under general anesthesia. Screw-type electrodes for VEP recording were fixed on the dura. ONH circulation, intraocular pressure (IOP), and blood pressure (BP) were measured after the passage of a current of 0.1 mA for 0.1 second (weak stimulation), 1 mA for 1 second (moderate), 5 mA for 10 seconds (strong), or 25 mA for 10 seconds (severe). Normalized blur (NB), indicative of tissue blood flow and velocity, was measured in the ONH after each stimulation, by using a laser speckle circulation analyzer. Changes in VEP and ocular fundus were also recorded. The ratio of cup area (CA) to disc area (DA) was measured before and 4 weeks after stimulation. After all experiments, the ONH was histologically examined. RESULTS: Weak stimulation increased NB in ONH for 10 minutes, whereas strong or severe stimulation significantly decreased NB for a longer time, in a dose-dependent manner. BP showed no significant change, except with severe stimulation. IOP was not significantly changed. VEP amplitude was reduced 30 minutes after strong stimulation. The CA-to-DA ratio was significantly increased 4 weeks after strong stimulation. In some rabbits, disc hemorrhage occurred, followed by enlargement of disc cupping, with slight gliosis. CONCLUSIONS: Electrical stimulation of the optic nerve changed ONH circulation and VEPs and increased disc cupping. This technique warrants further investigation as an experimental model for normal-tension glaucoma.

Cytotoxic effect of conjugated trienoic fatty acids on mouse tumor and human monocytic leukemia cells.

The cytotoxicity of fatty acids from seed oils containing conjugated linolenic acids (CLN) was studied. Fatty acids from pomegranate, tung, and catalpa were cytotoxic to human monocytic leukemia cells at concentrations exceeding 5 microM for pomegranate and tung and 10 microM for catalpa, but fatty acids from pot marigold oil had no effect at concentrations ranging up to 163 microM. The main conjugated fatty acids of pomegranate, tung, catalpa, and pot marigold were cis(c)9,trans(t)11,c13-CLN (71.7%), c9,t11,t13-CLN (70.1%), t9,t11,c13-CLN (31.3%), and t8,t10,c12-CLN (33.4%), respectively. Therefore, the cytotoxicities of fatty acids from pomegranate, tung, and catalpa were supposed to be due to 9,11,13-CLN isomers. To elucidate the cytotoxicity of these CLN, we separated each CLN isomer from the fatty acid mixtures by high-performance liquid chromatography and analyzed its cytotoxicity. The cytotoxicities of c9,t11,c13-CLN, c9,t11,t13-CLN, and t9,t11,c13-CLN were much stronger than that of t8,t10,c12-CLN. Therefore, the higher cytotoxicity of fatty acids from pomegranate, tung, and catalpa than those from pot marigold would be derived from the different activities of 9,11,13-CLN and 8,10,12-CLN. Since there was little difference in the cytotoxicities of c9,t11,c13-CLN,c9,t11,t13-CLN, and t9,t11,c13-CLN, it is suggested that the cis/trans configuration of 9,11,13-CLN isomers had little effect on their cytotoxic effects. The mechanism of the cytotoxicity of the four fatty acids above may involve lipid peroxidation, because the order of toxicity of the fatty acids was consistent with their susceptibility to peroxidation in aqueous phase. This was supported by the decrease in the cytotoxicity of the fatty acids by addition of butylated hydroxytoluene.

Eosinophilic pustular folliculitis (Ofuji's disease): indomethacin as a first choice of treatment.

Eosinophilic pustular folliculitis (EPF) is characterized by erythematous patches of large follicular papules and pustules involving mainly the face. Although various treatments have been attempted for EPF, including systemic and topical steroid, diaphenylsulphone, colchicine, minocycline as well as UVB phototherapy, there is no consensus on the first choice of treatment. We report a typical case and summarize 25 patients with EPF treated in our hospital between 1978 and 1998. Indomethacin was most frequently used (12/25) and showed clinical improvement in the majority of the cases (11/12). The effect of indomethacin was usually observed within 1--2 weeks after initiation of treatment. Decrease of peripheral blood eosinophils accompanied the clinical improvement. Thus, indomethacin should be considered as a first choice of treatment for EPF.

Citrus auraptene exerts dose-dependent chemopreventive activity in rat large bowel tumorigenesis: the inhibition correlates with suppression of cell proliferation and lipid peroxidation and with induction of phase II drug-metabolizing enzymes.

In our previous short-term experiment, Citrus auraptene inhibited the development of azoxymethane (AOM)-induced aberrant crypt foci, which are precursor lesions for colorectal carcinoma. In the present study, the possible inhibitory effect of dietary administration of auraptene was investigated using an animal colon carcinogenesis model with a colon carcinogen AOM. Male F344 rats were given s.c. injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce colon neoplasms. They also received diets containing 100 or 500 ppm auraptene for 4 weeks in groups of "initiation" feeding, starting 1 week before the first dosing of AOM. The diets containing auraptene were also given to rats for 38 weeks in groups of "postinitiation" feeding. At the termination of the study (38 weeks), dietary administration of auraptene caused dose-dependent inhibition in AOM-induced large bowel carcinogenesis. Auraptene feeding during the initiation phase reduced the incidence of colon adenocarcinoma by 49% at 100 ppm (P = 0.099) and 65% at 500 ppm (P = 0.0075). Auraptene administration during the postinitiation phase inhibited the incidence of colon adenocarcinoma by 58% at 100 ppm (P = 0.021) and 65% at 500 ppm (P = 0.0075). Also, the multiplicity of colon carcinoma was significantly reduced by initiation feeding at a dose level of 500 ppm (P < 0.01) and postinitiation feeding at a level of 100 and 500 ppm (P < 0.05 and P < 0.01, respectively). Feeding of auraptene suppressed the expression of cell proliferation biomarkers (ornithine decarboxylase activity and polyamine content) in the colonic mucosa and reduced the production of aldehydic lipid peroxidation [malondialdehyde and 4-hydroxy-2(E)-nonenal]. In addition, auraptene increased the activities of Phase II drug-metabolizing enzymes (glutathione S-transferase and quinone reductase) in the liver and colon. These findings suggest that the inhibitory effects of auraptene on AOM-induced colon tumorigenesis at the initiation level might be associated, in part, with increased activity of Phase II enzymes, and those at the postinitiation stage might be related to suppression of cell proliferation and lipid peroxidation in the colonic mucosa.

Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation.

The present study was carried out to examine the chemopreventive effects of carotenoids such as fucoxanthin, lycopene and lutein as well as curcumin and its derivative, tetrahydrocurcumin (THC), on development of putative preneoplastic aberrant crypt foci (ACF) in colons of mice initiated with 1,2-dimethylhydrazine dihydrochloride (DMH). Influence on proliferation of colonic crypt epithelial cells was also assessed in terms of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Five-week-old B6C3F1 male mice were divided into three groups, groups 1 and 2 being given DMH (20 mg/kg body wt, s.c.) twice a week for 3 weeks. Animals of group 1 were then treated with one of the test compounds, lycopene (0.005% and 0.0025%) or fucoxanthin (0.01%) in the drinking water and lutein (0.05%), curcumin (0.5%) or THC (0.5% and 0.2%) in the diet from weeks 5-12. Group 2 served as a carcinogen alone control and group 3 mice were given test compounds alone. All animals were killed at week 12. Numbers of ACF/mouse in the group 1 treated with fucoxanthin (47.1 +/- 13.7), lutein (42.6 +/- 19.6) or 0.5% THC (46.6 +/- 17.7) were significantly decreased as compared to the control group 2 value (63.3 +/- 19.4) (P < 0.01). Numbers of aberrant crypts (ACs)/mouse were also significantly lower after treatment with lutein (79.9 +/- 34.7) or 0.5% THC (81.8 +/- 32.5) than in the control group (115.1 +/- 37.1) (P < 0.01). BrdU labeling indices (LI) in mice treated with lutein and 0.5% THC were significantly decreased in both upper and lower half compartments of colonic crypts as compared to the controls (P < 0.05 and 0.01, respectively), especially the upper half data corresponding to reduction of ACs/mouse. The results thus suggest that fucoxanthin, lutein, and THC may have potential as chemopreventive agents against colon carcinogenesis.

Intrapancreatic accessory spleen diagnosed by technetium-99m heat-damaged red blood cell SPECT.

This is a report of accessory spleen located within the tail of the pancreas which mimicked a tumor. The correct diagnosis was made noninvasively with 99mTc-HDRBC (heat-damaged red blood cell) SPECT.

Mechanism of action of ginsenoside Rh2: uptake and metabolism of ginsenoside Rh2 by cultured B16 melanoma cells.

The uptake and metabolism of ginsenoside Rh2 (Rh2) by B16 melanoma cells were studied. In a medium containing 2% fetal calf serum, the uptake of Rh2 reached a maximum of 3 nmol/10(6) cells at 3-6 h after Rh2 (12.5 microM) was added, but gradually decreased to 0.8 nmol/10(6) cells. In these cells, protopanaxadiol (PPD), which is an aglycon of Rh2, increased inversely with the decrease in Rh2 as a result of deglycosylation by the cells. When PPD (8 microM) was added to the medium, the uptake reached a plateau of 2.4 nmol/10(6) cells, within 0.5 h. The association constant of Rh2 (1.74 +/- 1.08 x 10(6) M-1) for bovine serum albumin (BSA) was significantly higher than that of PPD (9.90 +/- 1.10 x 10(4) M-1). In a serum-free medium, both Rh2 and PPD were incorporated within 1.5 h. The uptake rate constant of Rh2 (1.20 +/- 0.20 h-1) was not significantly different from that of PPD (1.02 +/- 0.15 h-1), but the release rate constant of PPD (2.12 +/- 0.38 h-1) was significantly lower than that of Rh2 (3.03 +/- 0.57 h-1). These differences in affinity for BSA and the release rate constants were thought to be the cause of the difference in uptake kinetics between these drugs. The effects of Rh2 and PPD on the cells were identical, and there was no difference in the lag periods before the appearance of their effects, despite their differing rates of uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppressive effect of hyperbaric oxygenation on immune responses of normal and autoimmune mice.

We studied the effect of hyperbaric oxygenation (HBO) on immune responses in normal and autoimmune mice. Mice were exposed to HBO in an animal chamber at a pressure of 252.5 kPa for 1 h and once a day for 5 days. The immunization of C3H/He mice with sheep erythrocytes induced marked anti-sheep erythrocyte antibody response on day 7. However, this response was markedly suppressed in HBO-treated mice. The suppression is dependent on the duration of HBO and it works on the early and the late stage of antibody responses. HBO suppresses the development of both sheep erythrocyte-specific B cells and helper T cells after the immunization. Then, we tried to expose autoimmune mice to HBO. Spontaneous immunoglobulin production of NZB and MRL/lpr spleen cells was also significantly suppressed by HBO. Furthermore, long term HBO exposure results in the suppression of the development of autoimmune symptoms such as proteinuria, facial erythema and lymphadenopathy in MRL/lpr mice. All these results suggest that HBO is applicable for the treatment of autoimmune diseases.

[Induction of phenotypic reverse transformation by plant glycosides in cultured cancer cells].

Crude ginsenosides extracted from the root of Panax ginseng C.A. Meyer inhibited the growth and colony forming ability of Morris hepatoma cells in soft agar suspension culture, and stimulate the serum protein synthesis of these cells, thus converting the cell characteristics both functionally and morphologically to those resembling original normal liver cells. We have called such a phenomenon "reverse transformation" or "redifferentiation" which can be regarded as decarcinogenesis. In this report, the results of our recent investigations are presented with particular reference to reverse transformation of B16 melanoma cells induced by ginsenoside Rh2 isolated from the methanol extract of crude ginseng saponin fraction and action mechanisms of ginsenoside Rh2 are also discussed.