Extended one-generation reproductive toxicity study evaluating gardenia blue in Sprague Dawley rats.

Gardenia blue powder was administered at 0.5%, 2.5%, or 5.0% in feed to male and female Sprague Dawley rats in an Extended One-Generation Reproductive Toxicity Study (OECD Test Guideline 443). The dosed diet began 14 days before mating and was continued at the same concentration level for the entire study for all parental animals (P0) and offspring (F1). At weaning, offspring were allocated into one of 5 cohorts for different endpoints. P0 and F1 animals had blue urine, blue or black feces, and blue discolorations in gastrointestinal organs, mesenteric lymph nodes, and kidneys. This treatment-related finding was not considered adverse as there were no histopathologic correlates. There was a dose-related increase in sperm concentration in P0 and F1 males. There were dose-related increases in heart weights of F1 postnatal day (PND) 21 males, male and female thyroid weights, and female TSH levels of PND 91 F1 offspring, with no histopathological correlate. There were no consistent treatment-related adverse effects on any other parameters evaluated for general toxicity, reproductive toxicity, developmental neurotoxicity, or developmental immunotoxicity. The highest dietary concentration (5.0%) of gardenia blue powder was the no observed adverse effect level (NOAEL) for male and female rats at all life stages evaluated.

Twelve-month in utero safety assessment of gardenia blue, a natural food colorant.

Toxicity assessment of the food colorant Gardenia jasminoides Ellis at dietary exposures of 0.0%, 0.1%, 0.5%, 1.5%, 3.0% and 5.0% included measures of T-cell- dependent antibody response, neurotoxicity, and clinical and anatomic pathology in Sprague Dawley rats during mating, gestation, lactation, postnatal development, and following weaning for up to 12 months including 3- and 6-month interim evaluations. Blue coloration of the gastrointestinal tract, mesenteric lymph nodes and kidneys was present in treated rats only at necropsy with minimal blue coloration at the lowest dose and without histopathological correlates in any of the tissues. There was good survival with no consistent treatment-related changes in hematology, clinical chemistry, enhanced evaluation of lymphoid tissues, or tissue histopathology at interim and final time points. T-cell dependent antibody response and neurotoxicity screening were negative in treated rats. The no-observed-adverse-effect level (NOAEL) was determined to be 5.0% gardenia blue (2,854.5 and 3,465.4 mg/kg/day in parental males and females, respectively, prior to mating; 3,113.5 and 4,049.6 mg/kg/day in male and female offspring, respectively, following up to 12 months of exposure.

Chronic toxicity and carcinogenicity study of dietary gardenia blue in Sprague Dawley rats.

In this combined chronic toxicity/carcinogenicity study of gardenia blue as a natural food color additive, Sprague Dawley rats were administered 0.5%, 2.5%, or 5.0% gardenia blue via the feed or carrier diet (0.0% gardenia blue) for 12 (chronic toxicity cohort) or 24 (carcinogenicity cohort) months. No abnormal clinical, ophthalmological, neurotoxicity or clinical pathology changes were attributed to treatment, and there was no increase in mortality due to gardenia blue exposure. The only treatment-related change was grossly observed blue discoloration of the stomach, intestines, and mesenteric lymph nodes as well as reversible dark discoloration of the kidneys all without associated histopathology. The no-observed-adverse-effect level (NOAEL) for gardenia blue exposure via the diet for one or two years was determined to be 5.0% (2175.3 mg/kg body weight/day in male rats and 3075.4 mg/kg body weight/day in female rats).

[A Case of Breast Cancer in the Elderly Localized in the Nipple].

An 89-year-old woman presented to our clinic with a complaint of a wound in the left nipple. The pathological diagnosis via skin biopsy revealed adenocarcinoma. A physical examination, mammography, ultrasonography, and CT scan revealed a mass in the left nipple. However, a definite diagnosis could not be established by skin biopsy. Left breast-conserving surgery and sentinel lymph node biopsy were performed for diagnosis and treatment. Histological examination revealed a scirrhous type invasive ductal carcinoma in the left nipple and areola with skin invasion and lymph node metastasis. Radiation and hormone therapy were used as adjuvant therapy. She is alive with no local recurrence for 5 months post surgery. Since ductal carcinoma of the nipple is uncommon, we present this case report along with a review of the relevant literature.

Primary structure of gum arabic and its dynamics at oil/water interface.

Gum arabic (GA), an arabinogalactan-based gum, is a well-known powerful emulsifier. However, the poor stability of emulsion has often been pointed out. In order to clarify the origin, the structure-property relationship of GA, especially the interfacial property at oil/water interface, needs to be investigated. Here, we tried to correlate the primary structure with interfacial property at oil/water interface. A series of structural analyses by SEC-MALLS, SAXS, etc. showed that the primary structure of GA was a disk-like star shaped nanoparticle. The dynamic interfacial tension measurement showed that GA molecules adsorb onto oil surface in 2 steps: Firstly, the micron-aggregates of GA approach onto the oil surface, and then the aggregates are dissociated into nano-particles so that they cover the oil surface. Therefore, the emulsification and emulsion stability are controlled not by the property of the primary structure of GA but by the higher-order molecular network structure made of GA molecules.

[Cancer of the Ascending Colon Diagnosed at the Same Time as Breast Cancer Following Leukemia Treatment for Which Laparoscopic Surgery Was Performed-A Case Report].

An 83-year-old woman received 8 courses of chemotherapy(mogamulizumab)for adult T cell leukemia in the hematolo- gy department of our hospital, after which she achieved complete remission and was followed up with chemotherapy(VP/ MST: sobuzoxane/etoposide)as an outpatient. Later, diarrheal symptoms appeared, and detailed examinations led to a diagnosis of cancer of the ascending colon. Although no distal metastasis was found, breast cancer was also revealed in the C area of the right breast. The general status of the patient was favorable; thus, right pectoral muscle-conserving mastectomy and concomitant sentinel lymph node biopsy were performed through laparoscope-assisted extended right hemicolectomy. The postoperative course was favorable, and she was discharged on hospital day 7. The excised tumors were pathologically diagnosed as stageⅠ breast cancer and stage Ⅲa colorectal cancer. Chemotherapy(VP/MST)was administered without adjuvant chemotherapy. Presently, 18 months after surgery, complete remission of adult T cell leukemia has been maintained, without metastasis and recurrence of cancer of the ascending colon and breast cancer.

Body mass index and menopausal disorders during menopause affect vasomotor symptoms of postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes.

BACKGROUND: Adverse events related to endocrine therapies have a major impact not only on patients' quality of life but also on treatment discontinuation. Although vasomotor symptoms induced by aromatase inhibitors are frequently recognized, risk factors, especially for Japanese women, are not well reported. To identify risk factors for vasomotor symptoms of Japanese breast cancer patients treated with adjuvant anastrozole, we conducted a prospective cohort study based on patient-reported outcomes (PROs). PATIENTS AND METHODS: For this prospective cohort study (SAVS-JP, UMIN000002455), 391 postmenopausal Japanese estrogen receptor-positive breast cancer patients who were treated with adjuvant anastrozole were recruited from 28 centers. The PRO assessment was obtained from a self-reported questionnaire at baseline, 3, 6, 9 and 12 months between August 2009 and April 2012. Vasomotor symptoms, comprising hot flashes, night sweats, and cold sweats, were categorized into four grades (none, Grade 1: mild, Grade 2: moderate, Grade 3: severe). Pre-existing symptoms were only included if they had become worse than at baseline. RESULTS: Hot flashes, night sweats, and cold sweats at baseline were reported by 20.5, 15.1, and 8.2 % of the patients, respectively, and new appearance or worsening of symptoms in comparison with baseline by 38.4, 29.3, and 28.7 %, respectively. About 80 % of newly occurring symptoms were Grade 1, and less than 5 % were Grade 3. Vasomotor symptoms were reported by 201 out of 362 patients (55.5 %) during the first year and the mean time to onset was 5.6 months. Patients with vasomotor symptoms were significantly younger (mean 62.8 years, range 38-86 vs 64.7 years, range 37-84; p = 0.02), had higher body mass index (BMI) (23.4 kg/m2, range 15.8-39.9 vs 22.4 kg/m2, range 15.8-34.9; p = 0.01), had vasomotor symptoms sooner after menopause (12.4 years, range 0-51 vs 15.1 years, range 1-37; p = 0.002), and had more menopausal disorders during menopause (63.3 vs 36.7 %; p = 0.002). Multivariate analysis showed that BMI [odds ratio (OR) 1.09 per unit of increase, 95 % confidence interval (CI) 1.02-1.16; p = 0.009] and experiencing menopausal disorders (OR 2.11, 95 % CI 1.35-3.30; p = 0.001) were significantly associated with vasomotor symptoms. CONCLUSION: High BMI and experiencing menopausal disorders at menopause were found to be significantly associated with the occurrence of vasomotor symptoms. These findings are expected to prove useful for the management of postmenopausal Japanese women treated with aromatase inhibitors.

Risk factors for joint symptoms in postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes.

BACKGROUND: Endocrine treatment-related adverse events have a strong impact on patients' quality of life and sometimes result in treatment discontinuation. Since joint symptoms are the most frequently recognized side effect of aromatase inhibitors, evaluation of associated risk factors may yield significant findings. PATIENTS AND METHODS: A total of 391 postmenopausal Japanese women with estrogen receptor-positive breast cancer and treated with adjuvant anastrozole were enrolled from 28 centers for assessment of patient-reported outcomes (PROs) in this prospective cohort study (SAVS-JP, UMIN000002455). Patients completed the self-report questionnaire at baseline and after 3, 6, 9, and 12 months of treatment for evaluation of frequency of treatment-related joint symptoms (arthralgia, decrease in range of joint motion, and joint stiffness). RESULTS: We obtained PROs from 362 patients (92.6 %) at baseline and at one or more subsequent points. New or worsening from baseline of joint symptoms were reported by 260 patients (71.8 %). More than 90 % of the symptoms were mild or moderate and nearly 80 % had occurred by 6 months. Multivariate analysis showed that a short time span after menopause [odds ratio (OR) 0.95, 95 % confidence interval (CI) 0.90-0.99; P = 0.02] and adjuvant chemotherapy (OR 2.29, 95 % CI 1.06-4.95; P = 0.03) were significant independent risk factors for joint symptoms. No significant relationships between body mass index (BMI) and joint symptoms were identified. Eighteen patients discontinued treatment during the 1st year and eight of them reported joint symptoms. CONCLUSION: Taking into consideration that PROs may yield higher prevalence rates than physician ratings for symptoms published in pivotal clinical trials, we found that a short time span after menopause and use of adjuvant chemotherapy, but not high BMI, were significantly associated with joint symptoms. These findings might prove useful for counseling before initiating treatment with adjuvant aromatase inhibitors in postmenopausal Japanese women.

Lower photostability of capsanthin dispersed in an aqueous solution.

Food-additive grades of capsanthin, lutein, lycopene, and ß-carotene dispersed in aqueous solutions were photo-irradiated using a Xenon weather meter, and the levels of carotenoids were measured by HPLC and the absorbance method. Capsanthin photo-degraded more rapidly than the carotenoids tested, with less oxygen consumption. Unlike carotenes, capsanthin was partially converted into analogous colored compounds during degradation.

Photostability of lycopene dispersed in an aqueous solution.

Lycopene dispersed in aqueous solutions with different dissolved oxygen contents was photo-irradiated by using a xenon weather meter, and the contents of lycopene and dissolved oxygen were measured. Both the degradation of lycopene and the consumption of dissolved oxygen followed a first-order kinetics model. There was a proportional relationship between the degradation content of lycopene and the consumption of dissolved oxygen. These results indicate that dissolved oxygen would also be involved in the photolysis of lycopene.

[Equalization of breast cancer chemotherapy at general hospital( II )-evaluation of safety in FEC and TC regimens].

The safety of epirubicin (75 mg/m(2)), 5-fluorouracil (500 mg/m(2)) plus cyclophosphamide (500 mg/m(2)) (FEC75 therapy) and docetaxel (75 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) (TC therapy) every three weeks as neoadjuvant or adjuvant chemotherapy was evaluated. Six or 9 patients received FEC75 or TC therapy, respectively. The nadir of white blood cells and neutrocyte counts in FEC75 and TC therapy were after 11-15 days and 8-11 days of chemotherapy, respectively. On the other hand, those of monocyte and reticulocyte counts were after 8-11 and 4-8 days for FEC75 and TC therapy, respectively. This suggests that there is a lag time in these parameters for the evaluation of myelosuppression in each chemotherapy regimen, resulting in the prediction of the degree of myelotoxicity by these profiles. Although 2 patients who received TC therapy encountered febrile neutropenia, the symptoms were improved by quinolones, and so granulocyte colony-stimulating factor was not needed. In addition, remarkable non-hematological side effects were not observed, and, therefore, almost all chemotherapy was performed as scheduled. From these results, FEC75 and TC therapy are considered to be safe.

Hepatocyte growth factor improves survival after partial hepatectomy in cirrhotic rats suppressing apoptosis of hepatocytes.

BACKGROUND: Liver failure after hepatic resection is still a critical issue in the treatment of hepatic tumors in patients with liver cirrhosis. In the current study, the effect of hepatocyte growth factor (HGF) gene transfer, which is a multipotent growth factor, was examined in rats with liver cirrhosis that underwent 2/3 partial hepatectomy (PH). METHODS: Rats were treated with 1 mL of 1% dimethylnitrosoamine (DMN) 3 consecutive days per week for 4 weeks and then received a 2/3 PH. Three days before the PH, human HGF gene plasmid (20 microg) encapsulated in hemagglutinating virus of Japan (HVJ)-liposome was administered through a direct injection in the portal vein. Control cirrhotic rats received empty HVJ-liposome in the same manner. RESULTS: HGF gene transfer significantly improved survival after PH in the cirrhotic rats, and it stimulated BrdU uptake in hepatocytes. Although the HGF gene transfer did not change the liver regeneration rate after PH, it suppressed hepatocyte apoptosis and upregulated an antiapoptotic protein, Bcl-xl, but it did not affect the expression of Bax, which is a proapoptotic protein. CONCLUSION: HGF gene transfer to cirrhotic livers improves liver failure-associated death after PH upregulating expression of an antiapoptotic protein, Bcl-xl.

[A case report of autoimmune pancreatitis with Mikulicz' s disease and diabetes mellitus].

A 56-year-old man with bilateral swelling of lacrimal glands was admitted to our hospital. He was diagnosed as autoimmune pancreatitis with Mikulicz' s disease presenting the swelling of lacrimal glands, submandibular glands and the pancreas head and tail. Treatment with systemic prednisolone resulted in improvement of the swelling of these glands and pancreas. On the immunohistochemical examination, infiltration of CD4- and CD8-positive T lymphocytes was detected in the lacrimal gland, the submandibular gland, the gall bladder and the pancreas. Infiltration of IgG4-positive plasma cells was detected in the submandibular gland, the gall bladder and the pancreas. These results may suggest the presence of common etiology between autoimmune pancreatitis and Mikulicz' s disease.

Template-guided synthesis and individual characterization of poly(N-isopropylacrylamide)-based microgels.

We have succeeded in making cylindrical PNIPA-based microgels by a novel strategy in which template-guided synthesis and photochemical polymerization were combined. Cylindrical PNIPA-based microgels of relatively uniform sizes were easily obtained corresponding to the pore size of the template PC membranes. We have also individually characterized our PNIPA-based microgels by a laser trapping/Raman spectroscopy technique. On the basis of these results, the individual microscopic objects were confirmed to be PNIPA-based microgels.

Poly(N-isopropylacrylamide) microparticles produced by radiation pressure of a focused laser beam: a structural analysis by confocal Raman microspectroscopy combined with a laser-trapping technique.

We developed a confocal Raman microspectroscopy system combined with a laser trapping technique and applied it to aqueous solutions (H(2)O and D(2)O) of poly(N-isopropylacrylamide) (PNIPA), which is well-known as a representative thermo-responsive polymer, i.e., phase transition/separation between coiled and globular states. By introducing a near-infrared (1064 nm) laser beam into a microscope, PNIPA microparticles were produced at the focused spot of the laser beam, both in H(2)O and D(2)O. By using the present system, we succeeded in obtaining the Raman spectra of PNIPA in the coiled and globular states over a wide wavenumber region (800-3500 cm(-1)) for the first time. For the D(2)O solutions (in which the photothermal effect is negligible and hence the microparticles should be produced purely by the effect of radiation pressure), some significant differences were observed in the Raman spectra for the coiled state, in the globular state, and for laser induced microparticles. By analyzing these spectra in detail, we revealed that the structure of the laser-induced microparticles was analogous to that in the globular state. We also discuss the fundamental mechanism underlying the transformation of the higher order structure of a polymer by radiation pressure.