Soy protein intake increased bone mineral density under nonenergy-deficiency conditions but decreased it under energy-deficiency conditions in young female rats.

Many young individuals attempt to lose too much weight because of a false body image, which induces low bone mineral density (BMD) resulting from energy restriction. In addition, a decrease in estrogen has been observed along with the decrease in BMD. Estrogen is responsible for maintaining bone mass, and soybeans contain high levels of isoflavones, which have estrogen-like effects. Thus, we hypothesized that soy protein prevents low BMD caused by energy deficiency in young female rats. The purpose of this study was to examine the effect of soy protein intake on bone loss by energy deficiency in young female rats. Female Sprague-Dawley rats (6 weeks old) were randomly divided into the following 4 experimental groups: ad libitum feeding and casein diet (AL-Cas); ad libitum feeding and soy diet (AL-Soy); 40% energy restriction and casein diet (ER-Cas); and 40% energy restriction and soy diet (ER-Soy). The experimental period was 10.5 weeks. The AL-soy group had significantly higher BMD of the femur than the AL-Cas group (AL-Cas = 156 ± 5 mg/cm2, AL-Soy = 165 ± 7 mg/cm2; P < .05). Meanwhile, the ER-Soy group had significantly lower BMD of the tibia, femur, and lumbar spine than the ER-Cas group (ER-Cas = 147 ± 7 mg/cm2, ER-Soy = 133 ± 10 mg/cm2; P < .01). These results show that compared with ad libitum control groups, soy protein resulted in higher BMD under nonenergy deficiency, but under energy-deficiency conditions, it resulted in lower BMD.

Taurine Deficiency in Tissues Aggravates Radiation-Induced Gastrointestinal Syndrome.

Ionizing radiation administered for cancer treatment or from nuclear plant accidents are two common causes of radiation exposure. Ionizing radiation exposure generates reactive oxygen species and free radicals, which cause oxidative stress. We previously reported that taurine contributes to the recovery from radiation-induced injuries, suggesting its potential as a radioprotector and radiation mitigator. However, the effect of taurine on radiation-induced gastrointestinal syndrome remains poorly understood. The aim of this study was to examine the effect of taurine tissue depletion on radiation-induced gastrointestinal syndrome. Mouse models of radiation-induced gastrointestinal syndrome were established in TauT+/+ and TauT-/- mice by whole-body X-irradiation. We examined the 30-day survival rate, as well as the crypt-villus structure and proliferation of proliferating cell nuclear antigen (PCNA) + cells in the small intestine. The survival rate of TauT-/- mice was significantly lower than that of TauT+/+ mice. The villi in the small intestine of TauT-/- mice were significantly shorter than those in TauT+/+ mice. Additionally, there were significantly fewer PCNA+ cells in TauT-/- mice than in TauT+/+ mice. These data demonstrate that taurine is a key regulator of crypt stem cells and plays an important regulatory role in intestinal cell survival, proliferation, and fate. Therefore, taurine may reduce radiation-induced gastrointestinal syndrome.

Taurine and Its Anticancer Functions: In Vivo and In Vitro Study.

Taurine (2-aminoethanesulfonic acid) is a natural amino acid that is found widely in all mammalian tissues. Several studies have demonstrated that taurine has anti-inflammatory, antioxidant, and hypoglycemic effects. Recently, taurine not only mitigates the side effects of chemotherapy in cancer but also possesses antitumor properties, including inhibiting cancer cell proliferation and inducing apoptosis in certain cancers by differential regulating proapoptotic and antiapoptotic proteins. Antitumor studies of taurine are still in their infancy, and the mechanism of its antitumor effect is not fully understood. In this regard, it is worthwhile to study the antitumor mechanism of taurine, which may provide clues to develop new synthetic therapeutic molecules. In this mini review, we summarize the main effects of taurine that have shown suppressing actions in the initiation and progression of cancers. The underlying molecular mechanism also suggested that taurine can be a potential clinical application in tumor therapy. In addition, with the in-depth study of different biological functions of taurine, we found that many systemic diseases are associated with taurine. In this review, the research progress of taurine's antitumor effect is briefly summarized including the in vivo and in vitro studies in our laboratory.

Effects of Vitamin E on the immune system and tumor growth during radiotherapy.

PURPOSE: The purpose of this study is to evaluate the effects of Vitamin E (VE) on the immune system and tumor growth during radiotherapy (RT) in mice model. METHODS: C57BL/6NCrSlc mice were randomly distributed in four groups (control, VE alone, RT alone, and VE + RT). In the VE and VE + RT groups, VE was administered in the diet at 500 mg/kg. Radiation was delivered at 2 Gy in a single fraction on the whole body or at 6 Gy in three fractions locally in the RT and VE + RT groups. Changes in leukocytes and T lymphocytes were counted and compared between the four groups. To evaluate the effects on tumor growth, Ehrlich carcinoma cells were injected into the thighs of mice, and tumor volumes and growth inhibition rates were compared. RESULTS: The number of leukocytes was increased in the VE group compared with that in the control group. The magnitude of leukocyte recovery after RT was also increased by VE. This change was affected largely by alterations in lymphocytes and monocytes rather than that in granulocytes. Both CD4+ and CD8+ T lymphocytes were positively affected by VE. The tumor growth was inhibited not only by RT but also by VE alone. If RT was delivered with VE, tumor growth was markedly inhibited. CONCLUSION: VE could increase the number of leukocytes, primarily lymphocytes, even after RT was delivered. VE also inhibited the tumor growth in addition to RT. Thus, VE may be a useful radioprotective supplement in radiotherapy without inducing tumor growth.

Plant Enzymes Decrease Prostate Cancer Cell Numbers and Increase TNF-α In Vivo: A Possible Role in Immunostimulatory Activity.

Increased caloric intake and Westernized dietary choices may be contributing toward a recent rising trend of incidences of chronic lifestyle-related diseases. In this study, we evaluated the anticancer properties of Plant Enzyme Validux (PEV) using a mouse model. Five-week-old male C3H mice were randomly distributed into four experimental groups: Control, PEV only, 6Gy irradiation only, and PEV + 6Gy. PEV was orally administered daily at 500 mg/kg for 14 days prior to three rounds of 2Gy irradiation. We focused on the anticancer action and immunostimulatory effects of PEV with and without irradiation. Oncogene suppression was observed after PEV treatment as was an increase in TNF-α, suggesting an antitumor effect. PEV administration also appeared to reduce oxidative stress as evidenced by a decrease in lipid peroxidation. In addition, PEV confirmed radioprotective effect by radical blocking ability by radiation irradiation. Immunological responses to PEV administration were evidenced by an increase in number of total white blood cells and T lymphocytes. Immunotherapy is drawing more and more attention as a treatment for prostate cancer, suggesting that there will be a need for the identification of specific targets for prostate cancer and for more basic research on the genetic aspects of immunotherapy. Thus, PEV may be of use as a radioprotective supplement during radiotherapy for tumor treatment.

Protective Effects of Taurine on the Radiation Exposure Induced Cellular Damages in the Mouse Intestine.

There has been a growing interest in radiation effects as a result of the Fukushima nuclear power plant accident in 2011. Exposure to ionizing radiation causes oxidizing events to different organs such as the bone marrow, intestine, and kidney, which can result in radiation-induced injuries. Taurine (2-aminoethanesulfonic acid) is a sulfur-containing amino acid possessing several important physiological functions, including membrane stabilization, anti-oxidative activity, anti-inflammatory effects and modulation of intracellular calcium levels. Taurine appears to be an attractive candidate for use as a radioprotector and as a radiation mitigator, but its protection mechanism against radiation-induced cell damage is still unclear until now. In this review we describe some of the mechanisms explaining the radioprotective/mitigating effects of taurine on radiation-induced cellular damage and our recent findings on this subject.

The Potential Effects of Taurine in Mitigation of Radiation Nephropathy.

Taurine (2-aminoethanesulfonic acid) is a sulfur-containing organic acid possessing several important effects, including antioxidant and anti-inflammatory ones. Exposure to ionizing radiation generates free radicals and reactive oxygen species (ROS) in irradiated cells, and free radical generation leads to oxidative stress. It is known that radiation nephropathy includes an inflammation-based process in which ROS and cytokines are responsible. Different doses of explored radiation can cause apoptosis, inflammation and a profound oxidative stress in kidneys. Oxidative stress is involved in renal injury after exposure to both ionizing radiation and inflammation. In this review, we describe the protective effect of taurine against several kidney diseases and the potential effects of taurine in the mitigation of radiation nephropathy. We also report that X-irradiation decreased the expression of taurine and TauT in the kidney. Taurine administration suppressed the decrease in the expression of taurine and TauT in the kidney after radiation exposure. Taurine might contribute to the mitigation of kidney injury induced by radiation.

Cellular and Molecular Level Mechanisms against Electrochemical Cancer Therapy.

Electrochemical treatment (ECT) is a promising new way to induce tumor regression by flowing direct current into the cancer tissue. ECT was applied to different kinds of tumors in clinical studies and showed good results. In addition, basic research has almost not been done in the field of evaluation of efficacy, dose-response, and cytotoxicity. Therefore, the objective is to study the cellular mechanism in the antitumor effect of ECT and to contribute data of basic research of ECT. In the cell-level study, tumor cells (Sarcoma-180, Scc-7, Ehrlich Carcinoma) were studied using ICR mice and C3H mice. In the study group, pH values of control, 10mA × 150secs, 10mA × 300secs, and 10mA × 600secs groups were measured five times each. In histological level studies, ECT was performed on tumors inoculated on the upper part of the right foot of C3H mice. In each group, mice were sacrificed by cervical dislocation 6, 12, and 24 hrs after ECT treatment, and tumors were removed. The excised tumor was fixed in tissue with 10% formalin, and HE staining and apoptosis antibody staining were carried out from the obtained tissue section and observation. In the study at the cellular level, statistically significant differences were observed in all ECT groups in Sarcoma in the tumor growth measurement study compared with the control group. Statistically significant differences were also observed in Scc-7 in all ECT groups compared to the control group. In the intratumoral pH measurement study, there was a statistically significant difference between the anode and the cathode in each group compared to the control group. In the examination at the histological level, microscopic observation of a slide stained with apoptosis antibody with a magnification of 400 times showed that 6hrs after ECT it was stronger and then decreased. By performing ECT, a weak current flows in the living body. As a result, changes in tissue pH, generation of gas, etc. occur. In this study, it was also confirmed that the intratumor pH value becomes strongly acidic on the anode side and strongly alkaline on the cathode side. In addition, this study confirmed the occurrence of gas during treatment of ECT. Changes in the pH and the like cause changes in the environment in the cell, denaturation of proteins, apoptosis, and necrosis. In this study, a significant increase in apoptosis was confirmed in each ECT group compared to the control group. Treatment effects by ECT were also observed in tumor growth measurement studies and tumor weight measurement studies. From these research results, ECT is considered to be effective as a tumor treatment method.

Characteristics of Bone Strength and Metabolism in Type 2 Diabetic Model Nagoya Shibata Yasuda Mice.

We evaluated the suitability of Nagoya Shibata Yasuda (NSY) mice as an animal model for examining the influence of a glucose metabolism disorder on bone integrity, using Institute of Cancer Research (ICR) mice as controls. We selected six NSY and ICR mice each that were matched for weight, and measured serum glucose levels, serum insulin levels, and conducted an oral glucose tolerance test. Histological sections of the femurs of both mouse lines were prepared, and the bone strength, mass, and microstructure of the femur were compared, along with bone metabolism. Serum glucose levels were significantly higher in the NSY mice than in the control mice, but body weight and serum insulin levels did not differ between the groups. Bone mass, microstructure, and strength of the femur, and bone metabolism were lower in the NSY mice than in the control mice. In the cortical bone of the femur in the NSY mice, several parts were not stained with eosin, demonstrating a strong negative correlation between serum glucose levels and bone mineral density; however, there was a negative correlation between serum glucose levels and bone metabolic markers. The bone turnover rate in the NSY mice was decreased by hyperglycemia, resulting in a thinner and shorter femur, reduced cortical and trabecular areas, and lower bone mass compared to those of the control mice. Collectively, these results suggest deteriorated bone strength of the femur in NSY mice, serving as a useful model for studying the link between glucose metabolism and bone integrity.

Pharmaceutical Production of Anti-tumor and Immune-potentiating Enterococcus faecalis-2001 ß-glucans: Enhanced Activity of Macrophage and Lymphocytes in Tumor-implanted Mice.

BACKGROUND: Enterococcus faecalis 2001 is a probiotic lactic acid bacterium and has been used as a biological response modifier (BRM). From physiological limitation of bacterial preservation in storage and safety, the live E. faecalis 2001 has been heat-treated and the BRM components containing high level of ß-glucan, named EF-2001, were prepared. METHOD: The heat-treated EF-2001 has been examined for the antioxidative potential for radical scavenging and anti-tumor activities as well as immune-enhancing response in mice. Lymphocyte versus polymorphonuclear leukocyte ratio was increased in mice upon treatment with EF-2001. The number of lymphocytes was increased in the EF-2001-treated group. In the mice bearing two different Ehrlich solid and Sarcoma-180 carcinomas, the treatment with EF-2001 resulted in anti-tumor action. Tumor-suppressive capacity upon treatment with EF-2001 was significantly increased compared to normal controls. RESULTS: During the time interval administration of 5 weeks between the priming and secondary administration of EF-2001, the expression and production levels of TNF-α were also observed in the EF- 2001-administered mice. Additionally, anti-tumor activity examined with the intravenous administration of EF 2001 with a 34 times interval was also observed, as the growth of Sarcoma180 cells was clearly inhibited by the EF-2001. CONCLUSION: From the results, it was suggested that the immune response is enhanced due to antioxidative activity caused by the EF-2001 and anti-tumor activity by NK cells and TNF-α.

Taurine Administration Mitigates Cisplatin Induced Acute Nephrotoxicity by Decreasing DNA Damage and Inflammation: An Immunocytochemical Study.

Cisplatin (CDDP) is one of the most effective chemotherapeutic agent used in the treatment of many kind of solid tumors. Its primary side effect is nephrotoxicity. The aim of this study to investigate the effects of taurine on cisplatin-induced acute nephrotoxicity. A single intraperitoneal injection of CDDP (15 mg/kg, or 25 mg/kg) deteriorated the kidney functions as reflected by histopathological changes. Histopathological changes were observed in all cisplatin groups. In the cisplatin group, oxidative stress was evident in the cisplatin group by observing an increase in 8-OHdG expression, an indicator of oxidative DNA damage. CDDP also resulted to an increase in CD68 expression in the renal tissues of CDDP groups. Taurine transporter (TauT) was down-regulated, and p53 was up-regulated in renal tissues as indicated by immunohistochemical analysis. Administration with taurine prior to a cisplatin injection was able to protect against deterioration of kidney function, to abrogate the decline in anti-oxidants and to suppress the increase in DNA damage. Moreover, taurine inhibited p53 activation and improved the pathological changes induced by cisplatin. This study demonstrates the protective effects of taurine in attenuating the expression of pro-inflammatory mediators and in improving antioxidant capacity in the kidney of cisplatin-injected rats. Thus, taurine could be a beneficial dietary supplement to attenuate cisplatin induced nephrotoxicity.

Effect of Taurine on iNOS-Mediated DNA Damage in Drug-Induced Renal Injury.

Owing to an outstanding wide antitumor spectrum and excellent anti-tumor effect cisplatin has been used in chemotherapy for malignant tumor. However, cisplatin has strong side effects such as renal injury. Taurine has been found to protect against inflammatory tissue damage in a variety of experimental models. The aim of the present study was to investigate the effect of taurine against iNOS dependent DNA damage in cisplatin-induced renal injury in rats. With the help of a rat model of drug-induced kidney damage, we have assessed the nephrotoxic effects of different doses of cisplatin in the presence and absence of taurine. Immunohistochemical methods were used to examine the distribution of arginine, iNOS, citrulline and 8-nitroguanine in renal tissue. The expression levels of citrulline, iNOS, and 8-nitroguanine immunoreactivities were found to increase as a function of the dose of cisplatin used, and to decrease in the presence of taurine. The expression level of arginine immunoreactivity was reduced as a function of the dose of cisplatin used. On the other hand, iNOS, 8-nitroguanine and citrulline immunohistochemical staining showed an intense immunoreactivity in the renal tubule of cisplatin-treated animals; and arginine immunoreactivity was localized in the renal tubule of taurine-treated animals. We also confirmed the decrease of citrulline and iNOS expression in the renal tubule after taurine administration as well as the expression level of 8-nitroguanine, a nitrative stress marker in the same animals. The present results support the concept that taurine may have a protective role in the formation of cisplatin-related DNA lesions arising through iNOS-mediated nitrative stress.

Effect of Radiation on the Expression of Taurine Transporter in the Intestine of Mouse.

There has been a growing interest on the effects of radiation since the Fukushima nuclear power plant accident of 2011. Taurine has been reported to have a radioprotective effect in irradiated mice. However, the detailed mechanism of this radioprotective effect is still awaiting clarification. The aim of this study was to investigation how radiation affects the expression of taurine and to shed light on the mechanism accounting for radioprotective and radiation mitigating effect. Six-week-old male mice were randomly divided into two groups: IR group (7 Gy irradiation) and IR + Tau group (7 Gy irradiation + taurine 3000 mg/kg/day). We examined the survival rate, the expression of taurine and taurine transporter in the small intestine and the urinary taurine concentration. In this study, no statistically significant difference was found in the survival rate between IR Group and IR + Tau Group. Three days and 7 days after irradiation, the urinary taurine concentration of IR + Tau group increased more than that of IR group. Three days and 10 days after irradiation, the expression of taurine and taurine transporter in the small intestine of IR group and IR + Tau group decreased more than that of normal small intestine. It is reported that radiation exposure increases the urinary taurine concentration. We found that the radiation exposure decreases the expression of the taurine transporter in the small intestine of mouse. This finding suggests that a decrease in the expression of the taurine transporter promotes the release of taurine from the tissue into the urine.

T2-weighted magnetic resonance imaging of the liver: evaluation of the effect in signal intensity after Gd-EOB-DTPA enhancement.

OBJECTIVE: To evaluate the effect of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) on T2-weighted magnetic resonance imaging of liver parenchyma. METHODS: Forty-six patients with suspected hepatic tumors (group 1) underwent breath-hold T2-weighted fast spin echo imaging before and after 4 minutes of Gd-EOB-DTPA enhancement. Visual assessment and signal intensity (SI) measurements were performed to evaluate the effects of Gd-EOB-DTPA on the T2-weighted images of the liver. Thirteen healthy volunteers (Group 2) who underwent magnetic resonance imaging before and after 35 minutes of Gd-EOB-DTPA enhancement were also evaluated. RESULTS: In the qualitative analysis, visual SI of hepatic vessels after enhancement was significantly higher than that before enhancement (P < 0.001) in group 1, although there was no significant difference in the visual SI of liver parenchyma between before and after enhancement. In the quantitative analysis, SI ratio of liver parenchyma on enhanced images was significantly higher than that on unenhanced images (P < 0.001) in group 1. Conversely, the SI ratio (P < 0.001) and the visual SI (P = 0.008) in group 2 were significantly lower on the enhanced images than on the unenhanced images. CONCLUSIONS: The T2-weighted images obtained during the early phase after enhancement will appear similar to those of the unenhanced T2-weighted images, whereas later images will show a reduced signal of the liver parenchyma.

Apparent diffusion coefficient values in peripheral and transition zones of the prostate: comparison between normal and malignant prostatic tissues and correlation with histologic grade.

PURPOSE: To investigate the utility of apparent diffusion coefficient (ADC) values for discriminating tumor in patients with prostate cancer from normal prostatic tissues in healthy adult men, and to identify correlations between ADC and histologic grade of prostate cancer. MATERIALS AND METHODS: A total of 125 healthy male volunteers (mean age, 60 years; range, 50-86 years) and 90 prostate cancer patients (mean age, 71 years; range, 51-88 years) underwent diffusion-weighted imaging (DWI) of the prostate with a single-shot echo-planar imaging sequence using b-factors of 0 and 800 sec/mm2. ADC was measured from two locations in the peripheral zone (PZ) and two locations in the central gland (CG) in normal subjects, and tumor locations of PZ or transition zone (TZ) in patients with prostate cancer. RESULTS: Mean ADC values of tumor regions in both PZ (1.02+/-0.25x10(-3) mm2/sec) and TZ (0.94+/-0.21x10(-3) mm2/sec) were significantly lower than those in the corresponding normal regions (1.80+/-0.27x10(-3) mm2/sec and 1.34+/-0.14x10(-3) mm2/sec, respectively) (P<0.0001 each). Furthermore, a significant negative correlation was identified between ADC in PZ cancer and tumor Gleason score (rho=-0.497, P<0.0001). CONCLUSION: ADC values appear to provide acceptable diagnostic accuracy in both PZ and TZ.

Prostate cancer: relationships between postbiopsy hemorrhage and tumor detectability at MR diagnosis.

PURPOSE: To retrospectively evaluate the influence of postbiopsy hemorrhage on the accuracy of tumor detection at T2-weighted magnetic resonance (MR) imaging, dynamic contrast material-enhanced MR imaging, and diffusion-weighted (DW) MR imaging of prostate cancer, with histologic findings as the reference standard. MATERIALS AND METHODS: The institutional review board approved this study and waived the requirement for informed consent. Forty male patients aged 62-84 years (mean age, 71 years) who had prostate cancer underwent MR imaging of the prostate gland after ultrasonographically (US) guided systematic 12-core-specimen biopsy. The mean time between biopsy and MR imaging was 24 days (range, 6-54 days). T1-weighted, T2-weighted, dynamic contrast-enhanced, and DW imaging examinations were performed at 1.5 T. The prostate was divided, according to the biopsy sites, into eight regions on the MR images. Three reviewers in consensus evaluated each region for hemorrhage and prostate cancer. Statistical evaluations were performed with Mann-Whitney U, Ryan, and Spearman rank correlation tests. RESULTS: Intraglandular hemorrhage was observed in 38 (95%) patients and significantly more often in the peripheral zone (PZ) than in the transition zone (TZ) (P < .001). Degree of hemorrhage did not correlate significantly (P = .536) with time between biopsy and MR imaging. The sensitivity, specificity, and accuracy of combined T2-weighted, dynamic contrast-enhanced, and DW imaging in the diagnosis of prostate cancer were 69%, 85%, and 78%, respectively. Sensitivity and specificity were lower for the TZ than for the PZ. Degree of hemorrhage was significantly lower in regions of positive biopsy findings than in regions of negative biopsy findings (P = .001) and correlated negatively with tumor size (P = .043). CONCLUSION: Interpretation of combined T2-weighted, dynamic contrast-enhanced, and DW MR image findings can yield reasonable diagnostic accuracy in both the PZ (80% [191 of 240 regions]) and the TZ (74% [59 of 80 regions]).

Age-related and zonal anatomical changes of apparent diffusion coefficient values in normal human prostatic tissues.

PURPOSE: To identify age-related changes and differences in the diffusion of water molecules within the prostate, through diffusion-weighted imaging (DWI) of the prostate gland in healthy adult Japanese men. MATERIALS AND METHODS: A total of 114 healthy male volunteers (mean age, 55 years; range, 24-81 years) underwent DWI of the prostate with a single-shot echo-planar imaging (EPI) sequence using b-factors of 0 and 1000 seconds/mm(2). Apparent diffusion coefficient (ADC) values of six locations in the peripheral zone (PZ) and two locations in the central gland (CG) were measured and correlations between region and age were examined. RESULTS: ADC values measured within both PZ and CG regions of the prostate showed a uniform distribution, and no significant differences were found between evaluated regions. However, mean ADC values were 1.64 +/- 0.27 x 10(-3) mm(2)/second for PZ and 1.26 +/- 0.12 x 10(-3) mm(2)/second for CG, representing a significant difference. In addition, significant positive correlations were identified between ADC values for both PZ and CG regions and subject age (r = 0.526, P < 0.0001; r = 0.190, P = 0.0431, respectively). CONCLUSION: ADC values within both PZ and CG regions of the prostate increase with age, and this must be taken into consideration when using DWI in the diagnosis of prostate cancer.

Immune activation and radioprotection by propolis.

In this study, we focused on immune stimulation by Propolis, and examined changes in the effect of irradiation after Propolis administration. We also examined the radioprotective effect of Propolis by observing its effect on the immune system. The effect of immune activation by Propolis was investigated by measuring the total immunoglobulin (Ig) G and IgM. The radioprotective effect of immune activation by Propolis was investigated by measuring the T-lymphocyte subsets in the peripheral blood of mice following whole body irradiation. Compared with the control group, the IgG was significantly reduced in the Propolis group, indicating that Propolis suppressed IgG production. ELISA revealed that the amount of IgM in mouse serum was significantly higher in the Propolis group as compared with the control group, indicating that Propolis increased IgM production. The number of CD4-positive cells was increased only in the Propolis group. Likewise, the number of CD4-positive cells increased by 81% in the Propolis with irradiation group compared with the irradiation group alone. Compared with the control group, the Propolis group increased CD8-positive cells. Compared with the irradiation alone group, CD8-positive cells were decreased by Propolis with irradiation group. Propolis activated macrophages to stimulate interferon (IFN)-gamma production in association with the secondary activation of T-lymphocytes, resulting in a decrease in IgG and IgM production. Cytokines released from macrophages in mouse peripheral blood after Propolis administration activated helper T-cells to proliferate. In addition, activated macrophages in association with the secondary T-lymphocyte activation increased IFN-gamma production and stimulated proliferation of cytotoxic T-cells and suppressor T-cells, indicating the activation of cell-mediated immune responses.

Observation of microvasculatures in athymic nude rat transplanted tumor using synchrotron radiation microangiography system.

RATIONALE AND OBJECTIVES: The diagnostic potential of tumor microvasculatures with the monochromatic synchrotron radiation microangiography (MSRA) system was examined in an experimental model using athymic nude rats. MATERIALS AND METHODS: In the lower abdominal wall in athymic nude rats (male, 120-150 g, 6 weeks old), 1 x 10(7) cells of N-nitrosomethylurea-induced rat mammary adenocarcinoma was transplanted to prepare a lower abdominal wall tumor transplanted model. A microcatheter was inserted in the abdominal aorta in a rat under anesthesia, and microangiographic images of the normal inferior epigastric artery and vein were obtained using an MSRA system. Changes in the tumor microvasculatures were observed using an MSRA system on the day 7 (n = 3), day 14 (n = 3), day 21 (n = 3), and day 28 (n = 3) after transplant. In addition, we measured the microvessel density (MVD) with a computer using the binarization method. These results were compared among the histologic MVDs. RESULTS: The microvasculatures of tumors measuring 20-30 microm were observable by the MSRA system in the transplanted tumor model using the inferior epigastric artery and vein as the feeding vessels. The tumor microvasculatures were observed for 7-28 days after transplantation. The tumor MVD obtained by the binarization method increased as the tumor volume increased. When histologic MVD was compared with the fixed quantitative results of angiographic MVD, a significant correlation (r = 0.933, P <.01) was observed. CONCLUSION: These preliminary investigations indicate that MSRA proved to be suitable for quantification and appears to be a simple method for clearly imaging tumor microvasculatures.