Effect of Green Tea Extract Ingestion on Fat Oxidation during Exercise in the Menstrual Cycle: A Pilot Study.

In women, fat oxidation during exercise changes with the menstrual cycle. This study aimed to investigate the effect of green tea extract (GTE) ingestion on fat oxidation during exercise depending on the menstrual cycle phase. Ten women with regular menstrual cycles participated in this randomized, double-blind, crossover study. GTE or placebo was administered during the menstrual cycle's follicular phase (FP) and luteal phase (LP). Participants cycled for 30 min at 50% maximal workload, and a respiratory gas analysis was performed. Serum estradiol, progesterone, free fatty acid, plasma noradrenaline, blood glucose, and lactate concentrations were assessed before, during, and after the exercise. Fat oxidation, carbohydrate oxidation, and the respiratory exchange ratio (RER) were calculated using respiratory gas. Fat oxidation during the exercise was significantly higher in the FP than in the LP with the placebo (p < 0.05) but did not differ between the phases with GTE. Carbohydrate oxidation, serum-free fatty acid, plasma noradrenaline, blood glucose, and lactate concentrations were not significantly different between the phases in either trial. Our results suggest that GTE ingestion improves the decrease in fat oxidation in the LP.

[A Case of Malignant Lymphoma Undergoing HAI Treatment for Multiple Liver Metastases of Carcinoid That Appeared about Nine Years after Resection of Rectal Carcinoid with Liver Metastases].

The present case pertained to a 70-year-old woman. The fecal occult blood test was positive. Colonoscopyrevealed rectal cancer. She underwent the first operation of low anterior resection. Pathological diagnosis was carcinoid, se, ly2, v0, n1. Approximately2 months later, multiple liver metastases were found. Because of strong enhancement at angiography, transarterial chemoembolization(TACE)was selected. After 3 rounds of TACE, we operated the residual liver metastasis approximately1 year and 7 months after the first operation. However, approximately8 years and 9 months after the first operation, multiple liver metastases were found again. Hepatic arterial infusion(HAI)was chosen because tumors showed weak en- hancement on CT. First, we tried high-dose HAI(5-FU 1 g/dayat 1-3 and 5-7, amount: 6 g/week), and liver metastases was almost in CR. However, extrahepatic metastasis was found on PET-CT. Because of rapid growth, we operated the growing lymph node. Pathological diagnosis was diffuse large-cell type B-cell malignant lymphoma. Thus, we extended the interval of HAI(weekly, biweekly, and monthly)and simultaneously4 courses of R-THP-COP(R: rituximab, THP: pirarubicin, C: cyclophosphamide, O: vincristine, P: prednisolone)therapyfor malignant lymphoma was administered. She is now an outpatient. Liver metastases continue to be in CR at approximately1 year and the IL-2R value is almost within normal range.

[A Very Elderly Patient Successfully Treated by Multimodality Treatment for Pancreas Cancer with Synchronous Multiple Liver Metastases and Liver Dysfunction].

We report an 86-year-old patient successfully treated by multimodality treatment for advanced pancreatic cancer with synchronous multiple liver metastases and liver dysfunction. Systemic chemotherapy(SC)(gemcitabine[GEM]1 g and 5-FU 1 g biweekly)was initiated. Two weeks after, the radiation therapy(55 Gy/25 days)was added. Three weeks after, the short period's high dose hepatic artery infusion(SPHDHAI)(5-FU[1 g]×3 days: 1 day rest: 5-FU[1 g]×3 days)was started. By these treatments, liver dysfunction was completely improved and abdominal pain was disappeared. After 2 times of weekly high dose hepatic artery infusion(WHDHAI)(5-FU 1,500mg), the mixed chemotherapy(MC)(GEM 800 mg[systemic] and 5-FU 1,500 mg hepatic artery infusion:[HAI]biweekly)were started. She could live without admission for about 1 year. About 13 months after lung metastases was appeared and she died about 19 months after first chemotherapy. Our multimodality treatment(systemic and HAI therapy and radiation)was effective for keeping patient quality of life and for improving the survival even if the patient was a very old age and showed liver dysfunction.

[Two Year Recurrence Free Survival after Resection of Cutaneous Metastasis from Pancreatic Cancer - A Case Report].

The patient was a 73-year-old woman who underwent distalpancreatectomy for pancreas tailcancer (T3, N0, M0, stage III ). Hepatic arterialinfusion(HAI)using high-dose 5-fluorouracil(5-FU)(6,000mg/week)was performed 35 days after curative resection to prevent liver metastases. Although chemotherapy with gemcitabine(GEM)was administered for 2 weeks, the patient was aware of a nodule(1 cm in diameter)on the right lower quadrant of the abdomen. Resection of the cutaneous mass was performed and histological findings revealed metastatic adenocarcinoma from the pancreas cancer. Six courses of chemotherapy with GEM were administered as adjuvant therapy. Two years after the treatment with GEM, neurological symptoms appeared, and computed tomography(CT)and magnetic resonance imaging(MRI)revealed a solitary metastatic thalamus tumor(2 cm in diameter). After stereotactic radiotherapy, the patient was transferred to a different hospitalfor physicaltherapy. Herein, we report on a case of 2 year recurrence free survivalafter the resection of a cutaneous metastasis from pancreatic cancer.

[Efficacy of Combined Therapy(Drainage of the Bile Duct, High-Dose Hepatic Artery Infusion, and Radiation)for Hilar Cholangiocellularcarcinoma with Complete Portal Vein Obstruction].

We reported a case of hilar cholangiocellularcarcinoma with complete obstruction of the portal vein. The patient, who was a 65-year-old woman, suffered from fever and general fatigue as a result of acute cholangitis after insertion of a tube stent into the right bile duct. The main tumor was present on the right side of S1 and spread to both sides of the bile duct. S1 lobe was swollen and diffuse intrahepatic invasion was noted in the right lobe and S1. The portal vein was completely obstructed at the porta hepatis with a coronary vein-left renal vein shunt. We immediately administered a high-dose hepatic arterialinfusion( 5-FU 1 g×3 days: one day off 1 g×3 days)(HDHAI)to the right hepatic artery using a transient catheter insertion method. After 2 courses of HDHAI, the intrahepatic invasion decreased. However, after 4 courses of HDHAI(2 on the right side and 2 on the left side), the invasion on the left side of the IVC had increased. We then chose radiation therapy. Subsequently, transient cystic changes were observed; however, 4 months after radiation, the invasion on the left side of the IVC had regrown into the cardia. The patient suffered from vomiting as a result of the narrowing of the esophagus. We chose HDHAI and dilation of the esophagus using a balloon. Finally, the invasion on the left side of the IVC and S1 swelling decreased, and she could eat again. Thirteen months later, she remains an outpatient. We recommend HDHAI and radiation therapy to hilar cholangiocellularcarcinoma even if the portal vein is completely obstructed.

l-tyrosine induces melanocyte differentiation in novel pink-eyed dilution castaneus mouse mutant showing age-related pigmentation.

BACKGROUND: The mouse pink-eyed dilution (oculocutaneous albinism II; p/Oca2(p)) locus is known to control tyrosinase activity, melanin content, and melanosome development in melanocytes. Pink-eyed dilution castaneus (p(cas)/Oca2(p-cas)) is a novel mutant allele on mouse chromosome 7 that arose spontaneously in Indonesian wild mice, Mus musculus castaneus. Mice homozygous for Oca2(p-cas) usually exhibit pink eyes and beige-colored coat on nonagouti C57BL/6 (B6) background. Recently, a novel spontaneous mutation occurred in the progeny between this mutant and B6 mice. The eyes of this novel mutant progressively become black from pink and the coat becomes dark gray from beige with aging. OBJECTIVE: The aim of this study is to clarify whatever differences exist in melanocyte proliferation and differentiation between the ordinary (pink-eyed) and novel (black-eyed) mutant using serum-free primary culture system. METHODS: The characteristics of melanocyte proliferation and differentiation were investigated by serum-free primary culture system using melanocyte-proliferation medium (MDMD). RESULTS: The proliferation of melanoblasts in MDMD did not differ between the two mice. However, when the epidermal cell suspensions were cultured with MDMD supplemented with l-tyrosine (Tyr), the differentiation of black-eyed melanocytes was greatly induced in a concentration-dependent manner compared with pink-eyed melanocytes. Immunocytochemistry demonstrated that the expression of tyrosinase and tyrosinase-related protein-1 (Tyrp1) was greatly induced or stimulated both in pink-eyed and black-eyed melanocytes, whereas the expression of microphthalmia-associated transcription factor (Mitf) was stimulated only in black-eyed melanocytes. CONCLUSION: These results suggest that the age-related coat darkening in black-eyed mutant may be caused by the increased ability of melanocyte differentiation dependent on l-Tyr through the upregulation of tyrosinase, Tyrp1, and Mitf. This mutant mouse may be useful for animal model to clarify the mechanisms of age-related pigmentation in human skin, such as melasma and solar lentigines.

[Pre-Operative Treatment with Transcatheter Arterial Chemoembolization (TACE) and Hepatic Arterial Infusion (HAI) for Liver Metastasis from Gastric Cancer--A Case Report].

The patient was an 83-year-old man who underwent distal gastrectomy for gastric cancer (T3, N1, M0, P0, M0, stage ⅡB) at a different hospital from ours. A metastatic lesion was detected in the liver 5 months after gastrectomy. Although chemotherapy with S-1 or bi-weekly CPT-11 was administered for 6 months, the liver tumor increased in size. The patient was referred to our hospital for treatment of the liver metastasis. Abdominal-computed tomography (CT) and magnetic resonance imaging (MRI) revealed a solitary metastatic liver tumor (9 cm in diameter: S7/S6/S8) with a hypervascular tumor stain. Transcatheter arterial chemoembolization (TACE) using degradable starch microspheres (DSM) plus mitomycin C, and hepatic arterial infusion (HAI) using high-dose 5-fluorouracil (5-FU) (6,000 mg/week), were performed 54 days before curative resection of the liver (S6+S7+S8+S5b/c). Histological findings revealed metastatic adenocarcinoma with a tumor thrombus in the posterior branch of the portal vein. The patient was treated with 2 courses of adjuvant chemotherapy with paclitaxel. No recurrence was observed 8 months after hepatectomy. This case suggests that combined treatment with TACE/HAI as a multimodal treatment might be effective in the management of hypervascular liver metastasis from gastric cancer.

Beneficial effect of ubiquinol, the reduced form of coenzyme Q10, on cyclosporine nephrotoxicity.

BACKGROUND: Cyclosporine (CyA) nephrotoxicity is partly due to some oxidative stress. Ubiquinol, the reduced form of coenzyme Q10 (rCoQ10), has recently gained attention for its anti-oxidative potential. The aim of this study is to evaluate the effect of rCoQ10 on a CyA nephrotoxic rat model. MATERIALS AND METHODS: Six-week-old male Wistar rats were divided into three groups (five animals each). Group 1 received a medium only. Group 2 received 30 mg/kg/day of CyA only. Group 3 received both the same dose of CyA and 600 mg/kg/day of rCoQ10. CyA and rCoQ10 were both given orally for four weeks. Systolic blood pressure (BP), daily urinary albumin secretion (u-Alb), serum creatinine (s-Cr) level, and super-oxide anion (SO) level in the renal tissue were measured and compared among those three groups. Immunohistochemistry using an antibody for the transforming growth factor-beta (TGF-beta) was also examined. RESULTS: BPs, u-Albs, s-Crs, and SO levels of groups 1, 2, and 3 were 114 ± 3, 132 ± 4, and 129 ± 5 mmHg, 2.6 ± 0.5, 42.1 ± 7.2, and 22.8 ± 3.4 micro-g/day, 1.1 ± 0.2, 1.7 ± 0.2, and 1.3 ± 0.2 mg/dL, and 224 ± 84, 1251 ± 138, and 512 ± 109 RLU/g kidney respectively. U-Albs, s-Crs, and SO levels were signifi cantly ameliorated by rCoQ10. Micro-vacuolar changes and TGF-beta positive deposits in the proximal renal tubular cells of CyA group rats disappeared in those of CyA and rCoQ10 group rats. CONCLUSION: RCoQ10, an antioxidants, may have potential for preventing CyA nephrotoxicity.

Beneficial effect of ubiquinol, the reduced form of coenzyme Q10, on cyclosporine nephrotoxicity

BACKGROUND: Cyclosporine (CyA) nephrotoxicity is partly due to some oxidative stress. Ubiquinol, the reduced form of coenzyme Q10 (rCoQ10), has recently gained attention for its anti-oxidative potential. The aim of this study is to evaluate the effect of rCoQ10 on a CyA nephrotoxic rat model. MATERIALS AND METHODS: Six-week-old male Wistar rats were divided into three groups (five animals each). Group 1 received a medium only. Group 2 received 30 mg/kg/day of CyA only. Group 3 received both the same dose of CyA and 600 mg/kg/day of rCoQ10. CyA and rCoQ10 were both given orally for four weeks. Systolic blood pressure (BP), daily urinary albumin secretion (u-Alb), serum creatinine (s-Cr) level, and super-oxide anion (SO) level in the renal tissue were measured and compared among those three groups. Immunohistochemistry using an antibody for the transforming growth factor-beta (TGF-beta) was also examined. RESULTS: BPs, u-Albs, s-Crs, and SO levels of groups 1, 2, and 3 were 114 ± 3, 132 ± 4, and 129 ± 5 mmHg, 2.6 ± 0.5, 42.1 ± 7.2, and 22.8 ± 3.4 micro-g/day, 1.1 ± 0.2, 1.7 ± 0.2, and 1.3 ± 0.2 mg/dl, and 224 ± 84, 1251 ± 138, and 512 ± 109 RLU/g kidney respectively. U-Albs, s-Crs, and SO levels were significantly ameliorated by rCoQ10. Micro-vacuolar changes and TGF-beta positive deposits in the proximal renal tubular cells of CyA group rats disappeared in those of CyA and rCoQ10 group rats. CONCLUSION: RCoQ10, an antioxidants, may have potential for preventing CyA nephrotoxicity.

[Zhang-shu-zhen pharmacists' activities in the Qing dynasty].

Throughout the Qing dynasty, the commodity economy and domestic distribution in China developed dramatically. In this context, the market of Chinese medicines also expanded. At that time, the Zhang-shu-zhen pharmacists, in Jiangxi province, took the initiative in this market. This article explores their activities which were spread across China and it also examines the level of success or failure of their activities as well as the economical impact to the society of Zhang-shu-zhen. Due to its location between two important rivers that were used extensively for trade and their technical proficiency in pharmacy, Zhang-shu-zhen became an emporium of medicines. Nevertheless, many of the druggists were active in the southwest provinces of China. In order words, the activities of the druggists were coupled with the movement of immigration, from midland China to the southwest.

Rac1 GTPase in rodent kidneys is essential for salt-sensitive hypertension via a mineralocorticoid receptor-dependent pathway.

Hypertension is a leading contributor to cardiovascular mortality worldwide. Despite this, its underlying mechanism(s) and the role of excess salt in cardiorenal dysfunction are unclear. Previously, we have identified cross-talk between mineralocorticoid receptor (MR), a nuclear transcription factor regulated by the steroid aldosterone, and the small GTPase Rac1, which is implicated in proteinuric kidney disease. We here show that high-salt loading activates Rac1 in the kidneys in rodent models of salt-sensitive hypertension, leading to blood pressure elevation and renal injury via an MR-dependent pathway. We found that a high-salt diet caused renal Rac1 upregulation in salt-sensitive Dahl (Dahl-S) rats and downregulation in salt-insensitive Dahl (Dahl-R) rats. Despite a reduction of serum aldosterone levels, salt-loaded Dahl-S rats showed increased MR signaling in the kidneys, and Rac1 inhibition prevented hypertension and renal damage with MR repression. We further demonstrated in aldosterone-infused rats as well as adrenalectomized Dahl-S rats with aldosterone supplementation that salt-induced Rac1 and aldosterone acted interdependently to cause MR overactivity and hypertension. Finally, we confirmed the key role of Rac1 in modulating salt susceptibility in mice lacking Rho GDP-dissociation inhibitor α. Therefore, our data identify Rac1 as a determinant of salt sensitivity and provide insights into the mechanism of salt-induced hypertension and kidney injury.

Edaravone and carnosic acid synergistically enhance the expression of nerve growth factor in human astrocytes under hypoxia/reoxygenation.

Edaravone is a brain-penetrant free radical scavenger that is known to ameliorate postischemic neuronal dysfunction. The transcription factor Nrf2 plays an important role in the coordinated expression of stress-inducible genes. Here we examined the effects of edaravone and carnosic acid (CA), an Nrf2-inducer, on the expression of nerve growth factor (NGF) in human astrocytes exposed to hypoxia/reoxygenation. Cultured astrocytes were exposed to hypoxia for up to 4.5 h and then treated with edaravone and/or CA under normoxia (reoxygenation) for up to 72 h. Edaravone (∼1 mM) and CA (∼50 µM) treatment synergistically enhanced NGF expression. Nrf2 knockdown by siRNA and the inhibition of JNK (c-Jun N-terminal kinase) by SP600125 decreased both CA-induced NGF expression and Nrf2 nuclear accumulation and suppressed their synergistic effect on NGF expression. In contrast, the MEK (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase) inhibitor U0126 suppressed the synergism without inhibiting CA-induced NGF expression. These results suggest that the synergistic effects of CA and edaravone depend, at least partially, on JNK-dependent Nrf2 accumulation (induced by CA) and on MEK-dependent pathways (induced by edaravone). We conclude that the use of edaravone and CA in combination may have therapeutic potential in the treatment of brain damage, particularly ischemia/reperfusion injury.

Demonstration of aluminum in amyloid fibers in the cores of senile plaques in the brains of patients with Alzheimer's disease.

Aluminum (Al) exposure has been reported to be a risk factor for Alzheimer's disease (senile dementia of Alzheimer type), although the role of Al in the etiology of Alzheimer's disease remains controversial. We examined the presence of Al in the Alzheimer's brain using energy-dispersive X-ray spectroscopy combined with transmission electron microscopy (TEM-EDX). TEM-EDX analysis allows simultaneous imaging of subcellular structures with high spatial resolution and analysis of small quantities of elements contained in the same subcellular structures. We identified senile plaques by observation using TEM and detected Al in amyloid fibers in the cores of senile plaques located in the hippocampus and the temporal lobe by EDX. Phosphorus and calcium were also present in the amyloid fibers. No Al could be detected in the extracellular space in senile plaques or in the cytoplasm of nerve cells. In this study, we demonstrated colocalization of Al and beta-amyloid (Abeta) peptides in amyloid fibers in the cores of senile plaques. The results support the following possibilities in the brains of patients with Alzheimer's disease: Al could be involved in the aggregation of Abeta peptides to form toxic fibrils; Al might induce Abeta peptides into the beta-sheet structure; and Al might facilitate iron-mediated oxidative reactions, which cause severe damage to brain tissues.

[The effect of unsupervised home exercise program for patients with chronic obstructive pulmonary disease].

PURPOSE: This study assessed the effects of an unsupervised exercise training program at home on exercise function and health related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Forty-two patients with COPD (age 72.9+/-7.7 years; all males) were assigned to the exercise group (n=32) or the no-exercise group (n=10). The exercise group received a video recording of respiratory exercises to help them perform this program at home for six months. The no-exercise group did not receive any exercise program. The outcome measures were forced expiratory volume in one second (FEV(1)), vital capacity (VC), MRC dyspnea scale, 6 min walking distance (6MWD), shuttle walking distance (SWD), Borg scale and chronic respiratory disease questionnaire (CRQ) which includes four domains: dyspnea, fatigue, emotional function, and mastery. RESULTS: Patients completing this study consisted of: 19 patients in the exercise group, and 7 patients in the no-exercise group. Seventeen of the patients in the exercise group performed respiratory exercises every day for six months. We did not find any significant change in pulmonary function and dyspnea in either group. Significant improvements were achieved in 6MWD, SWD, CRQ (Dyspnea, Mastery) in the exercise group only. CONCLUSION: Our study suggested that unsupervised exercise training program at home consisting of respiratory exercise improved of exercise tolerance and HRQOL in patients with COPD.

[Legionella pneumonia which occurred in a private whirlpool bath user].

A 88 year old female with active rheumatoid arthritis treated by low dose of prednisolone and methotrexate was admitted to our hospital because of severe bilateral pulmonary infiltration and acute respiratory distress syndrome. On admission, she had consciousness disturbance and was intubated because of severe respiratory failure. We heard from her family of her habit she had taking a private whirlpool bath 2 or 3 times everyday. So, we suspected a Legionella pneumophila infection. We started intravenous erythromycin (EM) (1,500mg/day) and methylprednisolone pulse therapy (1,000mg x 3days) and full controlled mechanical ventilation supported with PEEP. Her respiratory failure was gradually improved and she was discharged on the 44 the hospital day. Legionella pneumophila (serogroup 6) was isolated in her sputum by B-CYE alpha culture. Legionella pneumophila (serogroup 6) was isolated in her private whirlpool bath too. Both samples revealed the same by genetic analysis with pulse field gel electrophoresis (PFGE). This is the first adult case of Legionella pneumophila pneumonia infected from a private whirlpool bath confirmed by genetic analysis. We should always suspect Legionella pneumonia as one of the severe community-acquired pneumonia, because Legionella pneumophila were frequently detected among various water sources including the private whirlpool bath.

Nuclear receptor agonists as potential differentiation therapy agents for human osteosarcoma.

PURPOSE: This study was designed to investigate whether nuclear receptor agonists can be used as potential differentiation therapy agents for human osteosarcoma. EXPERIMENTAL DESIGN: Four osteosarcoma cell lines (143B, MNNG/HOS, MG-63, and TE-85) were treated with proliferator-activated receptor (PPAR)gamma agonists, troglitazone and ciglitazone, and a retinoid X receptor (RXR) ligand, 9-cis retinoic acid. The proliferation and induction of apoptosis in the treated cells were assessed, as was the induction of alkaline phosphatase, a differentiation marker of osteoblasts. RESULTS: The expression of PPARgamma was readily detected in all tested osteosarcoma lines. On treatment with the PPARgamma and RXR ligands, all four osteosarcoma lines exhibited a significantly reduced proliferation rate and cell viability. Among the four lines, 143B and MNNG/HOS were shown to be more sensitive to ligand-induced apoptosis, as demonstrated by the Crystal Violet and Hoechst staining assays. Of the three tested ligands, troglitazone was shown to be the most effective in inducing cell death, followed by 9-cis retinoic acid. Moreover, a strong synergistic effect on the induction of cell death was observed when both troglitazone and 9-cis retinoic acid or ciglitazone and 9-cis retinoic acid were administered to osteosarcoma cells. Troglitazone was shown to effectively induce alkaline phosphatase activity, a well-characterized hallmark for osteoblastic differentiation. CONCLUSIONS: Our findings suggest that PPARgamma and/or RXR ligands may be used as efficacious adjuvant therapeutic agents for primary osteosarcoma, as well as potential chemopreventive agents for preventing the recurrence and metastasis of osteosarcoma after the surgical removal of the primary tumors.