Kampo medicines Rikkunshito and Hangeshashinto prevent cisplatin-induced intestinal mucosal injury in rats

Background/PurposeWe examined the effects and mechanisms of rikkunshito (RKT) and hangeshashinto (HST) on cisplatin-induced mucosal injuries in the rat small bowel.MethodsJuvenile rats were divided into 6 groups: sham control, cisplatin injection without kampo medicines, and cisplatin injection with oral administration of low and high doses of RKT (1000 mg/kg and 2000 mg/kg) and HST (500 mg/kg and 1000 mg/kg). Fecal condition, intestinal morphological changes, enterocyte proliferation, and enterocyte apoptosis were assessed.ResultsDiarrhea and atrophy of ileal villi observed in the cisplatin group were significantly improved in all kampo groups. Injury scores of the jejunum were significantly lower with RKT (2000 mg/kg) and HST (500 and 1000 mg/kg) than with cisplatin, and those of the ileum were significantly lower with HST (500 and 1000 mg/kg) than with cisplatin. Enterocyte proliferation of the jejunum was significantly increased with RKT (2000 mg/kg) and HST (500 mg/kg) compared with cisplatin, and those of the ileum were significantly increased in all kampo groups compared with the cisplatin group. Jejunal and ileal apoptosis following cisplatin administration was significantly inhibited by HST.ConclusionsRKT and HST prevented cisplatin-induced intestinal mucosal injury with increasing proliferation of intestinal epithelial cells. HST also attenuated cisplatin-induced crypt cell apoptosis.     

Effects of mechanical stretch on membrane currents of single ventricular myocytes of guinea-pig heart.

A technique to record whole cell membrane current during stretching single cardiac myocytes was developed. Ventricular myocytes were dissociated by treating guinea-pig hearts with collagenase. One end of the cell was fixed either to a microglasstool tip or to a glass plate, while the other end was attached either to a microglasstool tip or to a suction pipette, which was mounted on a micromanipulator. A time-independent current showing a reversal potential of -15 +/- 4 mV (n = 7) was activated when the myocytes were stretched more than 20% of the length between two fixed point. The current gradually relaxed during the maintained stretch, and disappeared on releasing the stretch. We failed to detect any consistent change in either the L-type Ca2+ current or the inward rectifier K+ current. For comparison, current changes induced by inflating the cell using a hypo-osmotic solution were recorded. The inflation was not accompanied by any change in the time-independent current. Instead, the delayed rectifier K+ current was increased to 170 +/- 48% control by the 70% hypo-osmotic solution. Thus, the effect of mechanical stretch on the time-independent current is different from those of hypo-osmotic cell inflation. The stretch-induced time-independent current is compared with reported current changes induced by the intracellular microinjection of Ca2+.     

Stereological estimation of mean nuclear volume in bladder cancer--measurement by point sampled intercepts

To obtain objective information about bladder cancer, we measured the mean nuclear volume of bladder cancer cells by using the "Point Sampled Intercepts" method, which was published by Gundersen et al. Thirty one cases of bladder cancer were selected and divided into 2 groups: group A; no recurrence over 3 years after initial TUR (12 cases), group B; cystectomy or cancer death (19 cases). Estimated mean nuclear volume was significantly smaller in group A than in group B. It is suggested that estimation of the mean nuclear volume by this stereological method may provide objective information for predicting the prognosis of patients with bladder cancers. Further studies in additional patients are required to substantiate the predictive potential of this method.     

Studies of effects of anticancer agents in combination with/without hyperthermia on metastasized human bladder cancer cells in chick embryos using the polymerase chain reaction technique

Cultivated T24 cells derived from a human bladder cancer were inoculated into the chorioallantoic membrane vein of chick embryos. Hyperthermic treatment was performed following injection of anticancer agents 3 days after the inoculation of the T24 cells. DNA samples were obtained from the livers of the chick embryos, and the polymerase chain reaction technique was used to amplify a DNA fragment specific to the human -globin gene. The Southern hybridization method was used to evaluate the inhibitory effects of anticancer agents in combination with/without hyperthermia on T24 cells metastasized to the liver. The hyperthermia exerted an inhibitory effect on the growth of the T24 cells in the livers of the chick embryos, and this was dependent on the thermal dose. The antitumor effects of hyperthermia performed at 42.5° C for 20 min and at 43.0° C for 10 min were evidenced by 69.2% an 82.0% inhibition of the growth of the metastasized T24 cells, respectively, as compared with the growth of untreated T24 cell. Hyperthermia performed at 42.5° C for 10 min alone produced 26.7% tumor growth inhibition, and these conditions for hyperthermia were subsequently used as a criterion for evaluating the effects of its combination with various anticancer agents. Adriamycin (20 g/egg) alone, mitomycin C (10 g/egg) alone, carboplatin (10 g/egg) alone, and cisplatin (10 g/egg) alone produced 13.5%, 58.9%, 27.3%, and 29.1% tumor growth inhibition, respectively. Adriamycin and mitomycin C applied in combination with hyperthermia showed additive inhibitory effects on the growth of the metastasized T24 cells in this chick embryo model.     

Complete nucleotide sequence of mouse mammary tumor virus from jyg chinese wild mice: Absence of bacterial insertion sequences in the cloned viral gag gene

Mammary tumors of a newly isolated strain of Chinese wild mouse (JYG mouse) harbor exogenous mouse mammary tumor virus (MMTV). The complete nucleotide sequence of exogenous JYG-MMTV was determined on the proviral 5' long terminal repeat (LTR)(partial)-gag-pol-env-3' LTR (partial) fragment cloned into a plasmid vector and the cDNA sequence from JYG-MMTV producing cells. Similarly to the other MMTV species the LTR of JYG-MMTV contains an open reading frame (ORF). The amino acid sequence of the JYG-MMTV ORF resembles that of SW-MMTV (92% identity) and endogenous Mtv-7 (93% identity) especially at the C-terminal region. Thus, a functional similarity in T-cell receptor V beta recognition as a superantigen is implicated among these MMTV species. Analysis of the viral gag nucleotide sequence revealed that this gene is not disrupted by the bacterial insertion sequence IS1 or IS2, which have been reported to be present in the majority of the plasmids containing the gag region. Comparison of amino acid sequences of JYG-MMTV with those of BR6-MMTV showed that over 96% of the amino acids of gag, pol, protease and env products are identical. These results suggest the intact nature of the nucleotide sequence of the near full-length MMTV genome cloned in the plasmid.     

Fish consumption and mortality from all causes, ischemic heart disease, and stroke: an ecological study.

BACKGROUND: The present study examined the relation between fish consumption and mortality from all causes, ischemic heart disease, and stroke. METHODS: The fish consumption data in 1961-1963, 1979-1981, and 1989-1991 and mortality data, age-standardized to 45-74 years, mean of the latest available 3 years, mostly around 1992-1993, in 36 countries, were obtained from the Food and Agriculture Organization and the World Health Organization, respectively. RESULTS: There exists an inverse univariate correlation between log fish consumption in 1961-1963, 1979-1981, and 1989-1991 and log all-cause (P < 0.01 to < 0.001) and ischemic heart disease (P < 0.05 to < 0.01) mortality in both sexes. An inverse univariate correlation between log fish consumption and log stroke mortality was found only for the period 1961-1963 in both sexes (P < 0.05). Log fish consumption was independently, significantly, and inversely associated with log all-cause (all P < 0.001), ischemic heart disease (P < 0.01 to < 0.001), and stroke (P < 0.05 to < 0.001) mortality in all three time periods in both sexes, after adjusting for confounding factors. These associations remained significant even after exclusion of Iceland and Japan, countries with the highest amount of fish consumption and the lowest all-cause mortality rate. CONCLUSIONS: Fish consumption is associated with a reduced risk from all-cause, ischemic heart disease, and stroke mortality at the population level.     

Synthesis of 18F-FDG with FDG MicroLab system: basic studies for clinical application

We synthesized 18F-FDG by using an automated synthetic apparatus "FDG MicroLab" (GE Medical Systems) which produces 18F-FDG by a solid phase 18F-fluorination. Its quality and reproducibility were evaluated in order to assess feasibility of the apparatus for routine clinical production of 18F-FDG. For 5 consecutive 18F-FDG synthesis, target irradiation was carried out at 15 microA for 60 min. 18F-FDG was obtained in 50 min after EOB with an end-of-synthesis yield of 9.34 +/- 1.06 GBq. Radiochemical yield and radiochemical purity were 47 +/- 3% (decay corrected) and 98.0 +/- 0.5%, respectively. Other several quality control parameters tested conformed with "Standards of Compounds Labeled with Positron Nuclides" (RADIOISOTOPES, 44, 1995). Thus, the automated synthetic apparatus "FDG MicroLab" has proven to stably produce 18F-FDG with high yield and high purity. The apparatus is feasible for routine clinical production of 18F-FDG.     

Clinical results and prognostic factors of radiotherapy for bone metastases from breast cancer

The purpose of this study was to analyze the results of initial radiotherapy for bone metastases (BM) from breast cancer and to investigate the prognostic factors. Between 1981 and 1995, 65 women (109 lesions) received initial radiotherapy for BM, aiming at a total dose of 50 Gy/25 Fr. Significant relief of pain was obtained in 61 (88.4%) of 69 estimable lesions according to the RTOG score. The control rates of pain including the prevention of pathological fractures or myelopathy were 80.4% at 5 years and 64.3% at 10 years. The median survival time of all patients was 11 months, and the survival rates were 56% at 1 year, 31.6% at 3 years, 17.9% at 5 years and 10.7% at 10 years, with five long-term survivors. Univariate analysis showed that a normal state of LDH, no other metastatic organs, a disease-free interval longer than two years, good performance status (0 or 1), BM limited to the axial bones, maintenance chemo-hormonal therapy and an age of more than 55 years were good prognostic factors. Multivariate analysis showed that LDH, age and performance status were significant predictors of prognosis. It is important to note the prognostic factors at the initial treatment of BM from breast cancer. We consider that further prospective studies are needed to determine the optimal treatment schedule, including radiotherapy and its combination with chemohormonal therapy, for BM.